The effect of cholinergic agonists on coronary flow rate and oxygen consumption in isolated perfused rat heart

1985 ◽  
Vol 17 (1) ◽  
pp. 31-42 ◽  
Author(s):  
E. Matti Nuutinen ◽  
David F. Wilson ◽  
Maria Erecińska
1990 ◽  
Vol 18 (4a) ◽  
pp. 497-510 ◽  
Author(s):  
Peter G. Anderson ◽  
Stanley B. Digerness ◽  
Jerald L. Sklar ◽  
Paul J. Boor

The isolated perfused rat heart model can be used to evaluate cardiotoxicity, and is especially useful in distinguishing direct vs indirect cardiac injury. Various perfusion systems can be used to characterize the pathophysiologic as well as morphologic changes induced by drugs or chemicals of interest. The isolated perfused heart was used in the studies described herein to characterize the mechanism of allylamine cardiotoxicity. Rat hearts were perfused with Krebs-Henseleit buffer containing 10 mm allylamine and a latex balloon was inserted into the left ventricle to monitor pressure. Coronary flow in hearts perfused with 10 mm allylamine was similar to control hearts at 5, 10, and 30 min, but was reduced by 1 hr (11.5 ± 0.6 ml/min/g wet heart weight vs 16.0 ± 0.7, p < 0.01). Peak left ventricular systolic pressure increased in hearts perfused with allylamine for 5 min (156 ± 8 mm Hg vs 103 ± 9, p < 0.01), but by 2 hr was decreased compared to controls (89 ± 6 vs 105 ± 5, p < 0.05). End diastolic pressure was markedly increased at 2 hr (58 ± 3 vs 4 ± 0.8, p < 0.01). Morphologically, allylamine perfused hearts exhibited significant contraction band changes as well as numerous cells with marked swelling of the sarcoplasmic reticulum. The findings in this study suggest that allylamine produces direct myocardial damage that appears to be independent of coronary flow. These studies demonstrate that the isolated perfused rat heart model can be used to evaluate mechanisms of acute cardiotoxicity.


1965 ◽  
Vol 209 (6) ◽  
pp. 1075-1080 ◽  
Author(s):  
Lionel H. Opie

The extracellular pH of the isolated perfused rat heart was varied from 6.9 to 8.0 usually by altering the bicarbonate content of the buffer. Isovolumic left ventricular contractility was measured by an intraventricular balloon. The peak systolic pressure was dependent on the coronary flow rate. At a constant flow rate the peak pressure and cardiac rate were unchanged at 7.4–8.0 but declined at about pH 7.1. The uptake and fate of pyruvate-1-C14 (6 mm) and palmitate-1-C14 (0.7 mm) were similar at pH 7.1–8.0. Compared with pH 7.4, oxidation rates of glucose-U-C14 (5 mm) and acetate-2-C14 (5 mm) were unchanged at pH 7.1, but were greater at pH 8.0. Other increases at pH 8.0 (glucose 5 mm) were in glucose uptake, lactate and pyruvate formation, and the percentage of the glucose uptake accounted for by the sum of C14O2, lactate, and pyruvate formed. It is concluded that in spite of decreased mechanical activity at pH 7.1, Krebs cycle activity is unaltered by pH changes from 7.1 to 8.0, whereas glycolysis and acetate oxidation increase above pH 7.4.


1977 ◽  
Vol 232 (4) ◽  
pp. H394-H399
Author(s):  
M. C. Kohn ◽  
D. Garfinkel

The behavior of a model for the partial depletion of adenine nucleotides in the perfused rat heart has been compared for ischemic and high coronary flow anoxic conditions. The accumulation of noradrenaline in the interstitial fluid greatly activates adenylate cyclase ultimately resulting in the degradation of 11.02 micronmol/g dry wt of ATP to adenosine, inosine, and hypoxanthine in 30 min. The high coronary flow rate during anoxic perfusion promotes washout of the noradrenaline from the interstitial fluid so that the hormone accumulates to only one fifth of its highest level in ischemia. This results in only slight activation of adenylate cyclase and in insignificant degradation of ATP in 2 min. The behavior of the model has been examined for two aerobic conditions--a transition from light to heavy work (2 min) and a transition from substrate-free to glucose perfusion (12 min), In both cases adenylate cyclase was not activated above its basal activity, and insignificant depletion of adenine nucleotides is predicted by the model.


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