Myocardial relaxation. I. Effect of nitroprusside on the tension prolongation phenomenon

The effects of nitroprusside and cyanide on myocardial relaxation were studied during hypoxia and reoxygenation of isolated rat papillary muscle, and during segmental ischemia and reperfusion in the intact dog heart. Nitroprusside did not affect isolated muscle performance before or during hypoxia. During reoxygenation of hypoxic muscles, the tension prolongation phenomenon (which characterizes abnormal or prolonged relaxation) was only slightly attenuated by the addition of nitroprusside to the muscle bath; in contrast, cyanide (at concentrations that did not prevent the return of tension) abolished tension prolongation during reoxygenation. During reperfusion of ischemic segments in intact hearts, the prolongation of segment tension was not affected by systemic administration of nitroprusside, but was abolished by intracoronary cyanide. Attenuation of the tension prolongation phenomenon by nitroprusside in the isolated muscle may be due to the liberation of cyanide. Inasmuch as nitroprusside did not affect the tension prolongation phenomenon in the intact heart, it is unlikely that the influence of this drug on left ventricular diastolic compliance is mediated through an alteration in the tension prolongation phenomenon.

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Abstract 1712: The P2Y 12 Antagonist Cangrelor and the GP IIb/IIIa Blocker Abciximab Reduce Platelet-Mediated Myocardial Injury After Ischemia and Reperfusion

Circulation ◽

10.1161/circ.118.suppl_18.s_374-b ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Jose A Barrabes ◽

Javier Inserte ◽

Maribel Mirabet ◽

Adoracion Quiroga ◽

Victor Hernando ◽

...

Keyword(s):

Myocardial Injury ◽

Myocardial Damage ◽

Left Ventricular ◽

Myocardial Salvage ◽

Ischemia And Reperfusion ◽

Activated Platelets ◽

Rat Hearts ◽

Developed Pressure ◽

Enddiastolic Pressure ◽

Isolated Rat

Objective: Platelets activated during experimental acute myocardial infarction (AMI) contribute to myocardial injury. We aimed to investigate whether platelets from patients with AMI increase myocardial damage after transient ischemia in isolated rat hearts and the modification of this effect by the P2Y 12 receptor antagonist cangrelor and the GPIIb/IIIa receptor blocker abciximab. Methods: Platelets were obtained from 9 AMI patients (7 thrombolyzed, all on aspirin) within 24 h after symptom onset. Incubation with 100 μM cangrelor or 50 μg/ml abciximab resulted, respectively, in 78 ± 4 and 90 ± 2% inhibition of aggregation (optical aggregometry). Isolated rat hearts (four simultaneous experiments per patient) were subjected to 40 min of global ischemia and 60 min of reperfusion. Hearts received no additional intervention (Control) or were infused during the 5 min prior to ischemia with platelets (22.5x10 6 /min), either untreated or treated with cangrelor or abciximab. Results: P-selectin expression (flow cytometry) in isolated platelets before infusion was 31 ± 3% (P = NS between groups). Platelets augmented myocardial injury, as demonstrated by worse left ventricular developed pressure (LVDevP), higher left ventricular enddiastolic pressure (LVEDP) and coronary resistance, and greater LDH release and infarct size (TTC staining), and both cangrelor and abciximab greatly attenuated these effects (Table ). Conclusions: Activated platelets from patients with AMI increase myocardial injury after ischemia and reperfusion, and cangrelor and abciximab attenuate this effect. The results support the notion that very early antiplatelet treatment may increase myocardial salvage by direct effects on the microcirculation in these patients.

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Effects of rate and rhythm on contraction of rat papillary muscle

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1959.197.6.1199 ◽

1959 ◽

Vol 197 (6) ◽

pp. 1199-1204 ◽

Cited By ~ 45

Author(s):

Brian F. Hoffman ◽

John J. Kelly

Keyword(s):

Cardiac Muscle ◽

Papillary Muscle ◽

Ionic Composition ◽

Force Frequency ◽

Progressive Decrease ◽

Plasma Epinephrine ◽

Perfusion Medium ◽

Frequency Relationship ◽

Rat Papillary Muscle ◽

Isolated Rat

The unusual relationship between frequency of contraction and tension developed by the isolated rat papillary muscle has been studied in detail. The progressive decrease in tension with increasing rate is unrelated to the size or weight of the muscle and is not changed by alterations in the ionic composition of the perfusion medium. The force-frequency relationship is also unchanged by addition of plasma, epinephrine or digitalis to the perfusion medium. Rat papillary muscle is similar to other preparations of cardiac muscle with respect to recovery of contractility and the development of rest contractions and postextrasystolic potentiation.

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Inhibition of contractile tension by capsaicin in isolated rat papillary muscle

General Pharmacology The Vascular System ◽

10.1016/0306-3623(95)00093-3 ◽

1996 ◽

Vol 27 (1) ◽

pp. 129-132 ◽

Cited By ~ 4

Author(s):

T. Yamato ◽

M. Aomine ◽

M. Ikeda ◽

H. Noto ◽

C. Ohta

Keyword(s):

Papillary Muscle ◽

Rat Papillary Muscle ◽

Isolated Rat

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Changes in LV papillary muscle performance and myosin composition with aortic insufficiency in rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1987.253.5.h1005 ◽

1987 ◽

Vol 253 (5) ◽

pp. H1005-H1011 ◽

Cited By ~ 1

Author(s):

C. S. Apstein ◽

Y. Lecarpentier ◽

J. J. Mercadier ◽

J. L. Martin ◽

F. Pontet ◽

...

Keyword(s):

Papillary Muscle ◽

Aortic Insufficiency ◽

Left Ventricular ◽

Muscle Performance ◽

Common Mechanism ◽

Velocity Of Shortening ◽

Isoenzyme Composition ◽

Myosin Isozyme ◽

Induced Changes ◽

Myocardial Adaptation

Aortic insufficiency was induced in rats. Left ventricular papillary muscle function was studied after 5, 12, and 40 wk and compared with the papillary muscles from sham-operated animals. The maximum unloaded velocity of shortening, Vmax, was decreased in the rats with aortic insufficiency relative to controls by 15, 20, and 34% at 5, 12, and 40 wk, respectively. The decrease in Vmax occurred concomitantly with a change in the myosin isoenzyme composition such that the V1 isoform content decreased and the V3 isoform increased. Relative to age-matched controls, the V3 content in the hearts with aortic insufficiency had increased by 80, 180, and 125% at 5, 12, and 40 wk, respectively. The decrease in Vmax in the aortic insufficiency group muscles correlated with the change in myosin isozyme composition and could not be explained by changes in collagen content. Thus aortic insufficiency induced changes in myosin isozyme content and Vmax similar to those previously observed with aortic stenosis, thus suggesting a common mechanism of myocardial adaptation to different types of mechanical overload.

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Changes in [Na+]i, compartmental [Ca2+], and NADH with dysfunction after global ischemia in intact hearts

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2001.280.1.h280 ◽

2001 ◽

Vol 280 (1) ◽

pp. H280-H293 ◽

Cited By ~ 51

Author(s):

Srinivasan G. Varadarajan ◽

Jianzhong An ◽

Enis Novalija ◽

Steven C. Smart ◽

David F. Stowe

Keyword(s):

Contractile Function ◽

Ischemia Reperfusion ◽

Left Ventricular ◽

Global Ischemia ◽

Contractile Dysfunction ◽

Ischemia And Reperfusion ◽

Mechanical Responses ◽

First Derivative ◽

Before And After ◽

Intact Heart

We measured the effects of global ischemia and reperfusion on intracellular Na+, NADH, cytosolic and mitochondrial (subscript mito) Ca2+, relaxation, metabolism, contractility, and Ca2+ sensitivity in the intact heart. Langendorff-prepared guinea pig hearts were crystalloid perfused, and the left ventricular (LV) pressure (LVP), first derivative of LVP (LV dP/d t), coronary flow, and O2 extraction and consumption were measured before, during, and after 30-min global ischemia and 60-min reperfusion. Ca2+, Na+, and NADH were measured by luminescence spectrophotometry at the LV free wall using indo 1 and sodium benzofuran isophthalate, respectively, after subtracting changes in tissue autofluorescence (NADH). Mitochondrial Ca2+ was assessed by quenching cytosolic indo 1 with MnCl2. Mechanical responses to changes in cytosolic-systolic (subscript sys), diastolic (subscript dia), and mitochondrial Ca2+ were tested over a range of extracellular [Ca2+] before and after ischemia-reperfusion. Both [Ca2+]sysand [Ca2+]dia doubled at 1-min reperfusion but returned to preischemia values within 10 min, whereas [Ca2+]mito was elevated over 60-min reperfusion. Reperfusion dissociated [Ca2+]dia and [Ca2+]sys from contractile function as LVPsys-dia and the rise in LV dP/d t (LV dP/d t max) were depressed by one-third and the fall in LV dP/d t (LV dP/d t min) was depressed by one-half at 30-min reperfusion, whereas LVPdiaremained markedly elevated. [Ca2+]sys-diasensitivity at 100% LV dP/d t max was not altered after reperfusion, but [Ca2+]dia at 100% LV dP/dtmin and [Ca2+]mito at 100% LV dP/d t max were markedly shifted right on reperfusion (ED50 +36 and +125 nM [Ca2+], respectively) with no change in slope. NADH doubled during ischemia but returned to normal on initial reperfusion. The intracellular [Na+] ([Na+]i) increased minimally during ischemia but doubled on reperfusion and remained elevated at 60-min reperfusion. Thus Na+ and Ca2+ temporally accumulate during initial reperfusion, and cytosolic Ca2+ returns toward normal, whereas [Na+]i and [Ca2+]mito remain elevated on later reperfusion. Na+ loading likely contributes to Ca2+ overload and contractile dysfunction during reperfusion.

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Different patterns of protein kinase C activation mediated by ui-adrenoceptor stimulation and phorbol ester in isolated rat left ventricular papillary muscle.

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)39598-8 ◽

1991 ◽

Vol 55 ◽

pp. 404

Author(s):

Hitoroi Otani ◽

Mitsuyoshi Hara ◽

Chiyoko Inagaki

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Phorbol Ester ◽

Papillary Muscle ◽

Left Ventricular ◽

Kinase C ◽

Protein Kinase C Activation ◽

Isolated Rat

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P2 purinergic receptor activation enhances cardiac contractility in isolated rat and mouse hearts

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2001.281.1.h334 ◽

2001 ◽

Vol 281 (1) ◽

pp. H334-H341 ◽

Cited By ~ 32

Author(s):

Qibing Mei ◽

Bruce T. Liang

Keyword(s):

Phospholipase C ◽

Receptor Agonist ◽

Positive Inotropic Effect ◽

Receptor Activation ◽

Left Ventricular ◽

P2x Receptor ◽

Inotropic Effect ◽

Isolated Rat ◽

Intact Heart

Activation of P2 purinergic receptors exerts a potent positive inotropic effect in the cardiac myocyte. However, it is unknown whether its activation can also cause an increased contractility in intact heart. With the use of isolated rat and mouse hearts, the objective of the present study was to investigate the effect of P2 receptor agonist on the function of the intact heart. In both Langendorff rat hearts and working rat and mouse heart models, the P2X receptor agonist 2-methylthio-ATP (2-meSATP) caused dose-dependent increases in left ventricular developed pressure, rate of contraction, and rate of relaxation. The extent of P2X receptor agonist-stimulated increase in contractility was significantly less than that stimulated by the β-adrenergic agonist isoproterenol. However, the increase in contractility occurred without a significant effect on the basal heart rate, in contrast to that caused by isoproterenol. In isolated rat ventricular myocytes, both ATP and the P2X receptor agonist 2-meSATP stimulated large increases in the myocyte contractile amplitude (107 ± 13% and 99 ± 9%, n = 17 cells from 5 rats and n = 19 cells from 6 rats, respectively). 2-meSATP caused only a slight increase in phospholipase C activity and could stimulate myocyte contractility in the presence of phospholipase C inhibitor U-73122, consistent with the role of a phospholipase C-independent P2X receptor in mediating the positive inotropic effect of 2-meSATP. The data provide evidence for a potentially important physiological role of the cardiac P2X receptor and for the concept that agonist at this receptor may be beneficial for the treatment of cardiac dysfunction.

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Protective Effect of Danshen During Myocaredial Ischemia and Reperfusion: An Isolated Rat Heart Study

The American Journal of Chinese Medicine ◽

10.1142/s0192415x90000046 ◽

1990 ◽

Vol 18 (01n02) ◽

pp. 19-24 ◽

Cited By ~ 55

Author(s):

W. Zhou ◽

T.J.C. Ruigrok

Keyword(s):

Flow Rate ◽

Coronary Flow ◽

Negative Inotropic Effect ◽

Left Ventricular ◽

Isolated Rat Heart ◽

Mechanical Activity ◽

Ischemia And Reperfusion ◽

Radix Salviae Miltiorrhizae ◽

Developed Pressure ◽

Isolated Rat

The effect of Danshen (Radix salviae miltiorrhizae) on mechanical activity and coronary flow rate if isolated rat hearts was examined to assess the ability of Danshen to protect the myocardium against the effects of ischemia and reperfusion. After 20 min of control perfusion, in the presence or absence of Danshen, the hearts were made totally ischemic for 30 min and then reperfused for 30 min. Danshen had a negative inotropic effect and caused an increase of coronary flow rate. During post-ischemic reperfusion recovery of left ventricular developed pressure in the pressure in the Danshen-treated hearts was significantly better and contracture was significantly less than in the untreated hearts. The results indicate that Danshen protects the heart against some of the deleterious effects of ischemia abd reperfusion.

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