The Effect of Ouabain on Substrate Metabolism in the Isolated Perfused Rat Heart

1971 ◽  
Vol 49 (5) ◽  
pp. 412-419 ◽  
Author(s):  
Robert J. Hoeschen

The effect of ouabain (2, 5, and 10 μg/ml) on the uptake and oxidation of 5 mM glucose-U-14C and 0.4 mM palmitate-1-14C was determined in the isolated perfused rat heart. During 30-min perfusions, 5 and 10 μg/ml ouabain enhanced glucose uptake and 10 μg/ml also increased glucose oxidation. Palmitate uptake, oxidation, and incorporation into tissue lipids were unaffected by ouabain. The addition of glucose did not alter the lack of effect of ouabain on palmitate metabolism, but the presence of palmitate inhibited the stimulatory effect of ouabain on glucose uptake. The ouabain enhancement of glucose uptake was not associated with any change in glycerol release from the perfused heart, nor did ouabain increase the stimulated glucose utilization due to insulin. The concentrations of ouabain used in these experiments were shown to have an inotropic effect when the glycoside was added after 45 min of control perfusion. Thus, ouabain had no effect on palmitate metabolism. The enhancement of glucose uptake and oxidation was not due to an antilipolytic effect, nor did ouabain potentiate the effect of insulin on glucose transport. The ouabain effect on glucose utilization was associated with, but not necessarily a result of, increased contractility.

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.


Physiology ◽  
1998 ◽  
Vol 13 (4) ◽  
pp. 203-210 ◽  
Author(s):  
Heinz-Gerd Zimmer

In 1866, Carl Ludwig together with Elias Cyon created the first isolated perfused frog heart preparation. Perfusion systems for the isolated mammalian heart were developed by H. Newell Martin in 1883 and by Oscar Langendorff in 1895. In its working mode, the isolated perfused rat heart was established in the 1960s.


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.


Sign in / Sign up

Export Citation Format

Share Document