scholarly journals Use of the Isolated Perfused Heart for Evaluation of Cardiac Toxicity

1990 ◽  
Vol 18 (4a) ◽  
pp. 497-510 ◽  
Author(s):  
Peter G. Anderson ◽  
Stanley B. Digerness ◽  
Jerald L. Sklar ◽  
Paul J. Boor
Keyword(s):  
Rat Heart ◽  
Coronary Flow ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Heart Weight ◽  
Isolated Perfused Heart ◽  
Heart Model ◽  
Perfused Heart ◽  
Perfused Rat Heart ◽  
Isolated Perfused Rat Heart

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.

The Isolated Perfused Heart and Its Pioneers

Physiology ◽  
1998 ◽  
Vol 13 (4) ◽  
pp. 203-210 ◽  
Author(s):  
Heinz-Gerd Zimmer
Keyword(s):  
Rat Heart ◽  
Frog Heart ◽  
Isolated Perfused Heart ◽  
Perfused Heart ◽  
Perfused Rat Heart ◽  
Isolated Perfused Rat Heart ◽  
Mammalian Heart ◽  
Heart Preparation ◽  
The 1960S

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.

Crystalloid and perfluorochemical perfusates in an isolated working rabbit heart preparation

1985 ◽  
Vol 249 (2) ◽  
pp. H285-H292 ◽  
Author(s):  
J. M. Chemnitius ◽  
W. Burger ◽  
R. J. Bing
Keyword(s):  
Cardiac Output ◽  
Coronary Flow ◽  
Systolic Pressure ◽  
Pressure Rise ◽  
Rabbit Heart ◽  
Left Ventricular ◽  
Heart Weight ◽  
Perfused Heart ◽  
Heart Preparation ◽  
Perfused Hearts

Krebs-Henseleit buffer (KH) and a perfluorochemical (FC-43) were compared as perfusates in an isolated working rabbit heart preparation. Both perfusates were oxygenated in an identical manner using an infant bubble oxygenator. After 60 min of perfusion, no difference could be detected in the ratio of wet to dry heart weight between KH- and FC-43-perfused hearts (KH, 6.25 +/- 0.3; FC-43, 5.99 +/- 0.20). Left ventricular systolic pressure, maximal rate of left ventricular pressure rise, mean aortic systolic pressure, cardiac output, aortic flow, left ventricular power, and myocardial O2 consumption (MVO2) were significantly higher in FC-43-perfused hearts throughout the time of perfusion. However, there were no differences in resistance to cardiac output and heart rate. In KH- and FC-43-perfused hearts, MVO2 and left ventricular power were closely correlated (KH, r = 0.793; FC-43, r = 0.831). Significantly higher coronary flow of KH-perfused hearts could be attributed to the lower viscosity of KH (1.05 Pa . s) compared with FC-43 (1.91 Pa . s). Increased O2 extraction during KH perfusion could not compensate for low O2-carrying capacity of KH buffer (345 compared with 705 nmol O2 X ml-1 in FC-43 emulsion). A postischemic increase of coronary flow was observed only in FC-43-perfused hearts (28%). These results demonstrate a different response of perfused heart preparations to FC-43 and KH buffer.

scholarly journals Anthrax edema toxin has cAMP-mediated stimulatory effects and high-dose lethal toxin has depressant effects in an isolated perfused rat heart model

2011 ◽  
Vol 300 (3) ◽  
pp. H1108-H1118 ◽  
Author(s):  
Caitlin W. Hicks ◽  
Yan Li ◽  
Shu Okugawa ◽  
Steven B. Solomon ◽  
Mahtab Moayeri ◽  
...  
Keyword(s):  
Rat Heart ◽  
Left Ventricular ◽  
Lethal Toxin ◽  
Heart Model ◽  
In Vivo Models ◽  
Inotropic Effects ◽  
Perfused Rat Heart ◽  
Isolated Perfused Rat Heart ◽  
Edema Toxin

While anthrax edema toxin produces pronounced tachycardia and lethal toxin depresses left ventricular (LV) ejection fraction in in vivo models, whether these changes reflect direct cardiac effects as opposed to indirect ones related to preload or afterload alterations is unclear. In the present study, the effects of edema toxin and lethal toxin were investigated in a constant pressure isolated perfused rat heart model. Compared with control hearts, edema toxin at doses comparable to or less than a dose that produced an 80% lethality rate (LD80) in vivo in rats (200, 100, and 50 ng/ml) produced rapid increases in heart rate (HR), coronary flow (CF), LV developed pressure (LVDP), dP/d tmax, and rate-pressure product (RPP) that were most pronounced and persisted with the lowest dose ( P ≤ 0.003). Edema toxin (50 ng/ml) increased effluent and myocardial cAMP levels ( P ≤ 0.002). Compared with dobutamine, edema toxin produced similar myocardial changes, but these occurred more slowly and persisted longer. Increases in HR, CF, and cAMP with edema toxin were inhibited by a monoclonal antibody blocking toxin uptake and by adefovir, which inhibits the toxin's intracellular adenyl cyclase activity ( P ≤ 0.05). Lethal toxin at an LD80 dose (50 ng/ml) had no significant effect on heart function but a much higher dose (500 ng/ml) reduced all parameters ( P ≤ 0.05). In conclusion, edema toxin produced cAMP-mediated myocardial chronotropic, inotropic, and vasodilatory effects. Vasodilation systemically with edema toxin could contribute to shock during anthrax while masking potential inotropic effects. Although lethal toxin produced myocardial depression, this only occurred at high doses, and its relevance to in vivo findings is unclear.

Buffer distribution in isolated perfused rat heart measured by rubidium 86

1964 ◽  
Vol 206 (4) ◽  
pp. 905-908 ◽  
Author(s):  
Joseph C. Shipp ◽  
James R. Spencer ◽  
Lamar E. Crevasse
Keyword(s):  
Coronary Artery ◽  
Coronary Arteries ◽  
Coronary Flow ◽  
Nonuniform Distribution ◽  
Isolated Perfused Heart ◽  
Perfused Heart ◽  
Perfused Rat Heart ◽  
Sintered Glass ◽  
Artery Flow ◽  
Millipore Filters

The pattern of distribution of Rb86 in sections of the isolated perfused heart was determined as a measure of uniformity of coronary artery flow. Results suggest that coronary flow was uniform after nonrecirculated perfusion for 15 min. Similar results were obtained in hearts perfused for 30 and for 60 min. The distribution of Rb86 was comparable in hearts perfused for 30 min with perfusate circulated through either coarse porosity, sintered-glass filters or 5-µ Millipore filters. A nonuniform distribution of isotope was demonstrated with ligation of branches of coronary arteries and with the introduction of air. The results suggest that hearts perfused by recirculation of buffer through coarse porosity, sintered-glass filters have a uniform distribution of perfusate throughout the heart.

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