Reduced oxygen supply explains the negative force-frequency relation and the positive inotropic effect of adenosine in buffer-perfused hearts

2005 ◽  
Vol 289 (1) ◽  
pp. H131-H136 ◽  
Author(s):  
Rodrigo M. Marin ◽  
Kleber G. Franchini
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Oxygen Supply ◽  
Positive Inotropic Effect ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Force Frequency ◽  
Frequency Relation ◽  
Perfused Hearts

In isolated rat hearts perfused with HEPES and red blood cell-enriched buffers, we examined changes in left ventricular pressure induced by increases in heart rate or infusion of adenosine to investigate whether the negative force-frequency relation and the positive inotropic effect of adenosine are related to an inadequate oxygen supply provided by crystalloid perfusates. Hearts perfused with HEPES buffer at a constant flow demonstrated a negative force-frequency relation, whereas hearts perfused with red blood cell-enriched buffer exhibited a positive force-frequency relation. In contrast, HEPES buffer-perfused hearts showed a concentration-dependent increase in left ventricular systolic pressure [EC50 = 7.0 ± 1.2 nM, maximal effect (Emax) = 104 ± 2 and 84 ± 2 mmHg at 0.1 μM and baseline, respectively] in response to adenosine, whereas hearts perfused with red blood cell-enriched buffer showed no change in left ventricular pressure. The positive inotropic effect of adenosine correlated with the simultaneous reduction in heart rate ( r = 0.67, P < 0.01; EC50 = 3.8 ± 1.4 nM, baseline 228 ± 21 beats/min to a minimum of 183 ± 22 beats/min at 0.1 μM) and was abolished in isolated hearts paced to suppress the adenosine-induced bradycardia. In conclusion, these results indicate that the negative force-frequency relation and the positive inotropic effect of adenosine in the isolated rat heart are related to myocardial hypoxia, rather than functional peculiarities of the rat heart.

Effect of Volatile Anesthetics on the Force–Frequency Relation in Human Ventricular Myocardium

2001 ◽  
Vol 95 (5) ◽  
pp. 1160-1168 ◽  
Author(s):  
Ulrich Schotten ◽  
Maura Greiser ◽  
Volker Braun ◽  
Christian Karlein ◽  
Friedrich Schoendube ◽  
...  
Keyword(s):  
Calcium Release ◽  
Negative Inotropic Effect ◽  
Volatile Anesthetics ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Force Frequency ◽  
Calcium Release Channel ◽  
Frequency Relation ◽  
Human Ventricular Myocardium

Background In human ventricular myocardium, contractile force increases at higher stimulation frequencies (positive force-frequency relation). In failing hearts, the force-frequency relation (FFR) is negative. Data on the effect of volatile anesthetics on FFR are very limited. Methods The authors obtained left ventricular tissue from 18 explanted hearts from patients undergoing cardiac transplantation and tissue of 8 organ donors. The negative inotropic effect of halothane, isoflurane, and sevoflurane on isometric force of contraction of isolated muscle preparations at a stimulation frequency of 1 and 3 Hz and the effect of each anesthetic on the FFR were studied. Ryanodine and verapamil were studied for comparison. In addition, the effect of the anesthetics on Ca(2+)-dependent (3)H-ryanodine binding was investigated. Results In nonfailing myocardium, halothane was the strongest negative inotropic compound, and the positive FFR was not affected by either drug. In failing myocardium, halothane also showed the strongest negative inotropic effect, but the positive shape of FFR was restored by halothane and ryanodine. In contrast, isoflurane, sevoflurane, and verapamil did not change FFR. Only halothane shifted the Ca(2+)-dependent (3)H-ryanodine binding curve toward lower Ca(2+) concentrations. Conclusion In nonfailing human myocardium, none of the anesthetics affect FFR, but halothane is the strongest negative inotropic compound. In failing myocardium, halothane, but not isoflurane or sevoflurane, restores the positive shape of FFR. Both the more pronounced negative inotropic effect of halothane and the restoration of the positive shape of FFR in failing myocardium in the presence of halothane can be explained by its interaction with the myocardial sarcoplasmic reticulum calcium-release channel.

Mechanisms underlying ischemic diastolic dysfunction: relation between rigor, calcium homeostasis, and relaxation rate

2003 ◽  
Vol 284 (3) ◽  
pp. H758-H771 ◽  
Author(s):  
Niraj Varma ◽  
James P. Morgan ◽  
Carl S. Apstein
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Coronary Flow ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Relaxation Cycle ◽  
Relaxation Velocity ◽  
Butanedione Monoxime ◽  
Length Changes ◽  
Severe Ischemia

Increased diastolic chamber stiffness (↑DCS) during ischemia may result from increased diastolic calcium, rigor, or reduced velocity of relaxation. We tested these potential mechanisms during severe ischemia in isolated red blood cell-perfused isovolumic rabbit hearts. Ischemia (coronary flow reduced 83%) reduced left ventricular (LV) contractility by 70%, which then remained stable. DCS progressively increased. When LV end-diastolic pressure had increased 5 mmHg, myofilament calcium responsiveness was altered with 50 mmol/l NH4Cl or 10 mmol/l butanedione monoxime. These affected contractility (i.e., a calcium-mediated force) but not ↑DCS. Second, quick length changes reversed ↑DCS, supporting a rigor mechanism. Third, ischemia increased the time constant of isovolumic pressure decline from 47 ± 3 to 58 ± 3 ms ( P < 0.02) but concomitantly abbreviated the contraction-relaxation cycle, i.e., pressure dissipation occurred earlier without diastolic tetanization. Finally, to assess any link between rate of relaxation and ↑DCS, hearts were exposed to 10 mmol/l calcium. Calcium doubled contractility and accelerated relaxation velocity, but without affecting ↑DCS. Thus ↑DCS developed during ischemia despite severely reduced contractility via a rigor (and not calcium mediated) mechanism. Calcium resequestration capacity was preserved, and reduced relaxation velocity was not linked to ↑DCS.

Effect of anemia on cardiac function, microvascular structure, and capillary hematocrit in rat hearts

2001 ◽  
Vol 280 (3) ◽  
pp. H1407-H1414 ◽  
Author(s):  
Karel Rakusan ◽  
N. Cicutti ◽  
F. Kolar
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Diastolic Pressure ◽  
Experimental Situation ◽  
Young Male ◽  
Left Ventricular ◽  
Male Rats ◽  
Capillary Length ◽  
Chronic Anemia ◽  
Cell Spacing

The effect of anemia on the coronary microcirculation was studied in young male rats. Chronic anemia resulted in increased left ventricular end-diastolic pressure and decreased functional reserve. Cardiac mass in anemic animals increased by 25%. Capillary and arteriolar densities in these hearts remained unchanged, indicating angiogenesis in this experimental situation (estimated aggregate capillary length in the left ventricle of anemic hearts was 3.06 km compared with 2.35 km in control hearts). Capillary hematocrit was decreased in chronic anemia less than systemic hematocrit: from 25 to 18% in anemia versus 45 to 28% in controls. Capillary hematocrit and red blood cell spacing were also studied after acute blood withdrawal. Here, capillary hematocrit was preserved even more: 22 versus 24% in systemic hematocrit. Finally, the same was studied in isolated hearts perfused with solutions of various hematocrits. After perfusion with low-hematocrit solution (14%), the capillary hematocrit (24%) was even higher than the perfusate hematocrit! In conclusion, we found evidence of angiogenesis in cardiomegaly induced by chronic anemia. Microvascular growth was accompanied by advantageous regulation of red blood cell spacing within these vessels. This was even more pronounced during acute hemodilution and in isolated perfused hearts.

P1718Veno-arterial ECMO versus Left Impella bleeding complications in cardiogenic shock patients on dual antiplatelet therapy

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Vandenbriele ◽  
J Wilson ◽  
A Baker ◽  
A Azzu ◽  
A Gambaro ◽  
...  
Keyword(s):  
Blood Cell ◽  
Cardiogenic Shock ◽  
Antiplatelet Therapy ◽  
Red Blood Cell ◽  
Dual Antiplatelet Therapy ◽  
Left Ventricular ◽  
Left Ventricular Failure ◽  
Ventricular Failure ◽  
Red Blood Cell Transfusions ◽  
Va Ecmo

Abstract Background Selective groups of patients, presenting with INTERMACS-1 cardiogenic shock due to acute ischaemic heart failure, may benefit from mechanical circulatory support (MCS). Patients with biventricular failure, severe septic shock or oxygenation problems should be selected for VA-ECMO, although the left Impella-CP heart pump can be considered as a less invasive alternative in supporting predominantly left ventricular failure. Bleeding issues are a major concern in patients on MCS, especially in this group where triple anticoagulation therapy (unfractionated heparin (UFH) for prevention of pump thrombosis and dual antiplatelet therapy (DAPT) after coronary stenting) is necessitated. We aim to investigate the bleeding and transfusion rate in DAPT-patients on VA-ECMO versus Impella. Methods We report single center data for 51 VA-ECMO and 8 Impella patients between 2011 and 2019. Indication for MCS was acute ischaemic cardiogenic shock. Patient demographics, transfusions and reported/radiographically diagnosed bleeding (BARC-classification) complications were analyzed. All patients received UFH and low dose aspirin plus clopidogrel or ticagrelor. Impella flow was at least 2.5 L/min. Transfusion targets were Hb >7 g/dl, fibrinogen >100 mg/dl (or >150 mg/dl when active bleeding) and platelet count >50/fL. Results Impella patients were significantly older (VA-ECMO 52.8 vs. Impella 62.4; p=0.02) as compared to the VA-ECMO group. Anti-Xa-levels and length of the MCS-run (mean 7.9 VA-ECMO vs. 6.4 days Impella) were comparable in both groups. Occurrences of minor bleeds was comparable between both groups (mainly oozing from the insertion site in the ImpellaTM group 63% vs. VA-ECMO 72%; p>0.05) but major bleedings with BARC score of 3 or more were significantly lower in the Impella group (13% vs. VA-ECMO 65%; p=0.005). Platelet and red blood cell transfusions were significantly lower in the Impella group (0.1 units of platelets per day vs. 1.1 units of platelets per day on VA-ECMO; p=0.002 and 0.8 units of RBCs per day vs. 2.6 units of RBCs per day on VA-ECMO; p=0.02). Bleeding/transfusion VA-ECMO vs Impella Conclusions Bleeding is a frequent complication of MCS. However, in our cohort, triple anticoagulation in acute cardiogenic shock due to ischaemic left ventricle failure resulted in a lower major bleeding rate when support was given by the left Impella device as compared with VA-ECMO therapy group. As a result, platelet and red blood cell transfusions were lower in the Impella group. These findings are likely to be partly explained by the increased number and size of cannulas in VA-ECMO, as well as the increased risk of haemolysis and consumptive coagulopathy due to the complexity and extensive foreign body surface of the ECMO-circuit. We conclude that Impella support should be considered as a safer option than VA-ECMO with regards to bleeding in patients with ischaemic left ventricular failure who require DAPT and MCS as a bridge to recovery or other definitive therapy.

Comparative effect of procainamide and lidocaine on myocardial contractility

1969 ◽  
Vol 47 (12) ◽  
pp. 1038-1042 ◽  
Author(s):  
M. Nahas ◽  
J. Lachapelle ◽  
G. M. Tremblay
Keyword(s):  
Myocardial Contractility ◽  
Positive Inotropic Effect ◽  
Negative Inotropic Effect ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Inotropic Effect ◽  
Comparative Effect ◽  
Heart Perfusion ◽  
Biphasic Effect ◽  
Therapeutic Doses

The effect of procainamide and lidocaine on myocardial contractility was studied in an isovolumic isolated rat heart perfusion preparation following the Langendorff technique. As a measure of myocardial contractility, the left ventricular intracavitary pressure and maximum dp/dt were determined and were found to be depressed proportionately to the dose of these agents. At the same concentration, lidocaine showed a more negative inotropic effect than procainamide (although the former seems clinically innocuous at therapeutic doses). In addition, procainamide produced in about one-half of the experiments a biphasic effect characterized by a slight transitory positive inotropic effect followed by a negative inotropic effect.

Interaction of Halogenated Anesthetics with α- and β-Adrenoceptor Stimulations in Diabetic Rat Myocardium

2004 ◽  
Vol 101 (5) ◽  
pp. 1145-1152 ◽  
Author(s):  
Julien Amour ◽  
Jean-Stéphane David ◽  
Benoît Vivien ◽  
Pierre Coriat ◽  
Bruno Riou
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Positive Inotropic Effect ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Diabetic Rat ◽  
Inotropic Effects ◽  
Beta Adrenoceptor ◽  
Alpha Adrenoceptor ◽  
Positive Inotropic Effects

Background Halogenated anesthetics potentiate the positive inotropic effects of alpha- and beta-adrenoceptor stimulations. Although diabetes mellitus induces significant myocardial abnormalities, the interaction of halogenated anesthetics and adrenoceptor stimulation in diabetic myocardium remains unknown. Methods Left ventricular papillary muscles were provided from healthy and streptozotocin-induced diabetic rats. Effects of 1 minimum alveolar concentration halothane, isoflurane, and sevoflurane on the inotropic and lusitropic responses of alpha (phenylephrine)- and beta (isoproterenol)-adrenoceptor stimulations were studied at 29 degrees C with 12 pulses/min. Data shown are mean percentage of baseline active force +/- SD. Results Phenylephrine induced comparable positive inotropic effects in healthy and diabetic rats (143 +/- 8 vs. 136 +/- 18%; not significant), but the potentiation by halogenated anesthetics was abolished in the diabetic rats (121 +/- 20, 130 +/- 20, and 123 +/- 20% for halothane, isoflurane, and sevoflurane, respectively; not significant). In diabetic rats, the positive inotropic effect of isoproterenol was markedly diminished (109 +/- 9 vs. 190 +/- 18%; P &lt; 0.05), but its potentiation was preserved with isoflurane (148 +/- 21%; P &lt; 0.05) and sevoflurane (161 +/- 40%; P &lt; 0.05) but not with halothane (126 +/- 16%; not significant). Halothane induced a deleterious effect on the sarcoplasmic reticulum, as shown by its impairment in the lusitropic effect of isoproterenol, compared with isoflurane and sevoflurane. Conclusion Potentiation of the positive inotropic effect of alpha-adrenoceptor stimulation by halogenated anesthetics is abolished in diabetic rats. In contrast, potentiation of beta-adrenoceptor stimulation is preserved with isoflurane and sevoflurane but not with halothane, probably because of its deleterious effects on sarcoplasmic reticulum.

Halothane Restores the Altered Force-Frequency Relationship in Failing Human Myocardium

1995 ◽  
Vol 82 (6) ◽  
pp. 1456-1462. ◽  
Author(s):  
Ulrich Schmidt ◽  
Robert H. G. Schwinger ◽  
Michael Bohm
Keyword(s):  
Cardiac Surgery ◽  
Human Heart ◽  
Positive Inotropic Effect ◽  
Negative Inotropic Effect ◽  
Human Myocardium ◽  
Inotropic Effect ◽  
Force Frequency ◽  
Beta Adrenoceptors ◽  
Frequency Relationship

Background The terminally failing human myocardium exerts a negative force-frequency relationship (FFR), whereas a positive FFR occurs in nonfailing myocardium. To study the possibility of pharmacologically influencing this defect of the failing human heart, the effect of halothane on the basal FFR and the FFR in the presence of isoproterenol and ouabain was investigated. Methods Experiments were performed on isolated, electrically driven (0.5-2 Hz, 37 degrees C, Ca2+ 1.8 mmol/l) ventricular preparations. Myocardium from human failing and nonfailing hearts was obtained at cardiac surgery. To further characterize the studied myocardium, the positive inotropic effect of isoproterenol and the density of beta-adrenoceptors were measured using the radioligand 125I-CYP. Results Halothane produced a negative inotropic effect. The anesthetic (0.38 mmol/l) reversed the negative FFR in failing myocardium, antagonized the effect of isoproterenol (0.1 mumol/l) on FFR, and restored the FFR in the presence of ouabain. Conclusions Halothane restores the FFR in human failing myocardium possibly by influencing the intracellular Ca2+ homeostasis. These findings provide evidence that pharmacologic interventions, e.g., during anesthesia, may influence contractility also as a result of a depressed or enhanced FFR.

scholarly journals Constraints on vertebrate athleticism: The temperature dependence of red blood cell volume

2013 ◽  
Author(s):  
James JF Gillooly ◽  
Rosana Zenil-Ferguson
Keyword(s):  
Blood Cell ◽  
Cell Volume ◽  
Red Blood Cell ◽  
Oxygen Supply ◽  
The Body ◽  
Whole Body ◽  
Activity Levels ◽  
Aerobic Activity ◽  
Highly Active ◽  
Athletic Ability

The ability to perform at high levels of aerobic activity (i.e. athletic ability) increases with temperature among vertebrates. These differences in species’ activity levels, from highly active to sedentary, are reflected in their ecology and behavior. Yet, the changes in the cardiovascular system that allow for greater oxygen supply rates at higher temperatures, and thus greater activity levels, remain unclear. Here we show that vertebrates provide more oxygen to tissues at higher temperatures in part by increasing the total volume of red blood cells in the body. Across 60 species of vertebrates (fishes,amphibians, reptiles, birds and mammals), whole-body red blood cell volume increases exponentially with temperature after controlling for effects of body size and taxonomy. These changes are accompanied by increases in relative heart mass, an indicator of athletic ability. The results help explain how temperature-dependent changes in cardiovascular design allow species to overcome the constraints of passive diffusion on oxygen supply.

scholarly journals Cardiotoxins from cobra Naja oxiana change the force of contraction and the character of rhythmoinotropic phenomena in the rat myocardium

2019 ◽  
Vol 487 (5) ◽  
pp. 578-583
Author(s):  
A. S. Averin ◽  
M. E. Astashev ◽  
T. V. Andreeva ◽  
V. I. Tsetlin ◽  
Yu. N. Utkin
Keyword(s):  
Positive Inotropic Effect ◽  
Stimulation Frequency ◽  
Inotropic Effect ◽  
Force Frequency ◽  
Rat Myocardium ◽  
Frequency Range ◽  
High Concentration ◽  
Irreversible Damage ◽  
Frequency Relationship ◽  
Positive Force

The study of the influence of cobra Naja oxiana cardiotoxins on the contractility of the rat papillary muscles and its rhythm-inotropic characteristics has that the presence of toxins induces a slight contractility decrease in the stimulation frequency range up to 0,1 Hz. In the stimulation frequency range from 0,1 to 0,5 Hz a positive inotropic effect is found. However, the positive inotropic effect is replaced by a negative one with further increase in the frequency up to 3 Hz. In the presence of cardiotoxins, the positive force-frequency relationship in the region of 1-3 Hz, characteristic of healthy rat myocardium, disappears and relationship becomes completely negative. L‑type calcium channel blocker nifedipine does not affect the changes induced by toxins, while a high concentration (10 mM) of calcium prevents the effects of cardiotoxins on the muscle. The results obtained show that the impairment of the force-frequency relationship occurs long before the development of irreversible damage in the myocardium and may be the first sign of the pathological action of cardiotoxins.

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