Effects of a new 1,3-thiazole Derivative ZSY-39 on force of contraction and cyclic AMP content in canine ventricular muscle

1990 ◽  
Vol 4 (4) ◽  
pp. 1127-1134 ◽  
Author(s):  
Masao Endoh ◽  
Hiroshi Satoh ◽  
Ikuo Norota ◽  
Katsuhisa Hirano
1956 ◽  
Vol 187 (1) ◽  
pp. 122-134 ◽  
Author(s):  
Marion deV. Cotten ◽  
Edmund Bay

Direct measurements of changes in the force of ventricular contraction with the strain gauge arch represent a sample of changes in the force of contraction of the entire ventricular muscle under conditions of an intact circulation. The responses of any given area of the ventricular muscle to repeated injections of the same dose of a cardiac stimulant drug are consistently similar. Further, there is a linear relationship between changes in the force of contraction as measured with the strain gauge arch and changes in the duration of the isometric pressure gradient. A direct relationship also exists between changes in contractile force and changes in stroke work. The relative advantages and limitations of the strain gauge arch and of the heart lever system, equipped with a strain gauge coil, are discussed in detail. Evidence is presented to show that the strain gauge arch is most useful in experiments in which substantial changes in the size of the heart do not occur. The heart lever system should be employed in experiments in which the size of the heart does undergo substantial change since adjustment may be made for changes in the initial diastolic fiber length. The time relations existing between direct recordings of contractile force made with the strain gauge arch and recordings of intravascular pressures have been demonstrated. A substantial portion of the contractile force is developed during the isometric phase of systole. There is a direct relationship between the amount of left ventricular contractile force developed during the isometric phase of contraction and the aortic diastolic pressure. A similar direct relationship exists between the total amount of contractile force measured by an arch on the left ventricle and the aortic systolic pressure. Mechanical stretching of the segment of muscle between the two points of attachment of the strain gauge arch produced length-tension curves which showed that a marked increase in contractile force occurs with increases in length of up to 40–60%. Stretching beyond these limits results in a progressive decrease in contractile force. The depth to which the sutures used in the attachment of the arch to the heart penetrated the myocardium has a moderate, but limited, quantitative influence upon the magnitude of contractile force measured. An arch attached with sutures penetrating deeply into the muscle measures more contractile force than an arch attached to the heart by superficially placed sutures.


1999 ◽  
Vol 202 (19) ◽  
pp. 2595-2607 ◽  
Author(s):  
D. Willoughby ◽  
M.S. Yeoman ◽  
P.R. Benjamin

We have used a combination of biochemical and pharmacological techniques to investigate the role of the cyclic nucleotides, 3′, 5′-cyclic adenosine monophosphate (cyclic AMP) and 3′,5′-cyclic guanosine monophosphate (cyclic GMP), in mediating the cardioregulatory effects of FMRFamide and other neuropeptides encoded on exon II of the FMRFamide gene of Lymnaea stagnalis. The ‘isoleucine’ peptides (EFLRIamide and pQFYRIamide) produced complex biphasic effects on the frequency, force of contraction and tonus of the isolated heart of L. stagnalis, which were dependent on adenylate cyclase (AC) activity of the heart tissue. At a control rate of cyclic AMP production of less than or equal to 10 pmoles min(−)(1)mg(−)(1) protein, the ‘isoleucine’ peptides produced a significant increase in AC activity in heart membrane preparations. This suggested that the enhanced AC activity is responsible for the stimulatory effects of the ‘isoleucine’ peptides on frequency and force of contraction of heart beat. This excitation sometimes followed an initial ‘inhibitory phase’ where the frequency of beat, force of contraction and tonus of the heart were reduced by the ‘isoleucine’ peptides. Hearts that showed the inhibitory phase of the ‘isoleucine’ response, but characteristically lacked the delayed excitatory phase, were found to have high levels of membrane AC activity (breve)10 pmoles min(−)(1)mg(−)(1) protein in controls. Application of the ‘isoleucine’ peptides to membrane homogenate preparation from these hearts failed to increase AC activity. The addition of FMRFamide produced significant increases in the rate of cyclic AMP production in the heart membrane preparations, which could account, at least in part, for the cardioexcitatory effects of this peptide in the isolated whole heart. A membrane-permeable cyclic AMP analogue (8-bromo-cyclic AMP) and an AC activator (forskolin) were also cardioexcitatory. The peptide SEEPLY had no effects on the beat properties of the isolated heart and did not alter AC activity. The activity of the membrane-bound (particulate) guanylate cyclase (GC) was not significantly affected by any of the peptides.


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