Experimental Heart Failure due to Inhibition of Utilisation of High-Energy Phosphates

Fleckenstein, A.; Döring, H. J.; Kammermeier, H.

doi:10.1159/000388373

Cited by 13 publications

(7 citation statements)

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“…The improvement in the myocardial depression during verapamil toxicity with isoproterenol is consistent with results obtained from papillary muscle preparations by Fleckenstein (14,23) in which the negative inotropic effects of verapamil were reversed with isoproterenol. The other sympathomimetic agents with beta adrenergic activity also produced hemodynamic improvement.…”

Section: Discussionsupporting

confidence: 90%

Treatment of verapamil toxicity in intact dogs.

Gay¹,

Algeo²,

Lee³

et al. 1986

J. Clin. Invest.

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The treatment of verapamil toxicity was examined in lightly sedated dogs. Verapamil, administered as a bolus (0.72 mg/kg) followed by a continuous infusion (0.11 mg/kg per min), decreased cardiac output (CO) from 3.1±0.1 to 1.7±0.1 liter/min (P < 0.001), heart rate (HR) from 85±4 to 57±3 beats/min (P < 0.001), left ventricular derivative of pressure with respect to time (LV dP/dt) from 2,085±828 to 783±78 mm Hg/s (P < 0.001), mean aortic pressure (AO) from 77±4 to 38±2 mm Hg (P < 0.001) and stroke volume from 39±3 to 28±2 ml/beat (P < 0.01). In verapamil-toxic animals isoproterenol increased HR, CO, LV dP/dt, and AO, calcium chloride increased LV dP/dt and AO; norepinephrine, epinephrine, and dopamine increased CO, AO, and LV dP/dt, atropine increased HR, CO, and AO. Phenylephrine (13-55 ,ug/kg per min) produced no changes except a small increase in AO while very high dose phenylephrine (300 Ag/kg per min) increased AO, CO, and LV dP/dt. 4-Aminopyridine (4-AP) increased HR, CO, LV dP/dt, and AO. When administered prior to verapamil, 4-AP prevented the development of verapamil toxicity as shown by the significantly higher AO (P < 0.001), CO (P < 0.01), and LV dP/dt (P < 0.01) when 4-AP followed by verapamil was compared to verapamil alone. In conclusion, there does not appear to be a single specific therapy for verapamil toxicity, however it can be partially corrected by presently available pharmacologic therapy and 4-AP.

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Section: Discussionsupporting

confidence: 90%

Treatment of verapamil toxicity in intact dogs.

Gay¹,

Algeo²,

Lee³

et al. 1986

J. Clin. Invest.

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“…He postulated that there are two molecular classes of heart failure: (1) those in which the defect lies in energy production, and (2) those in which the defect lies in energy utilization. During the intervening years several studies have supported this hypothesis; 4 -' however, some reports indicating normal energy metabolism in the failing heart also have appeared. Thus the molecular mechanisms underlying the loss of contractility in heart failure remain obscure and it commonly is held that biochemical defects are dependent on the type and degree of heart failure.…”

mentioning

confidence: 99%

Abnormalities in heart membranes and myofibrils during bacterial infective cardiomyopathy in the rabbit.

Tomlinson¹,

Lee²,

Dhalla³

1976

Circulation Research

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SUMMARY We studied hearts from sham-operated and uninfected catheterized rabbits as well as from rabbits at early and late stages of cardiomyopatny and failure after 3 and 6 days of infection with Streptococcus viridans. No ultrasrructural abnormalities or biochemical changes in membrane and myofibrillar activities were seen in 3-day uninfected hearts. ID 6-day uninfected hearts there were decreased sarcolemmal M >+ ATPase, Na + -K + ATPase, adenylate cydase and calcium binding, microsomal calcium binding and uptake, and myofibrillar Ca 1+ -stimulated ATPase as well as increased mitochondria! calcium uptake. Slight ultrastructural changes also were apparent in 6-day uninfected hearts. At both early and late stages of infective cardiomyopatfay and failure there were varying degrees of depression in sarcolemmal Mg I+ ATPase, Na + -K+ ATPase, adenylate cydase and calcium binding, microsomal calcium binding, calcium uptake and basal ATPase, and myofibrillar Ca 1+ -stimulated ATPase activities. However, sarcolemmal Ca'+ ATPase and myofibrillar Mg'+ ATPase activities were decreased only after 6 days of infection. Mitochondrial calcium binding and uptake were increased in early stages but decreased in late stages of disease. Furthermore in infected hearts there were defects in mitochondrial respiration and pbosphorylation. Generalized severe myocardial cell damage involving myofibrils, mitochondria, and the sarcotubular system was seen only in late stages of infection. The results demonstrate impairment of different membrane and contractile protein functions as well as ultrastructural abnormalities in bacterial cardiomyopathic hearts which were absent or of lesser magnitude in hearts with only hypertrophy. The findings reported here suggest to us that there is an association between heart failure and changes in function of cellular components during bacterial infective cardiomyopathy.CONGESTIVE HEART FAILURE is the major cause of death in patients with infective endocarditis. In previous studies we demonstrated that Streptococcus viridans induces endocarditis and myocardial dysfunction in rabbits and that clinical evidence of heart failure occurs in 100% of cases. 1 -* However, no information is available concerning the biochemistry of cardiac muscle, particularly with respect to This study was supported by the Manitoba Heart Foundation and is taken from the thesis submitted by Charles W. Tomlinson to the University of Manitoba for the Ph.D. degree in physiology. Dr. Tomlinson is the recipient of a Medical Scientist Award from the Canadian Heart Foundation.Address for reprints: Naranjan S. Dhalla, Ph.D., F I.C., Professor of Physiology, Experimental Cardiology Laboratory, Faculty of Medicine, University of Manitoba Winnipeg, Manitoba, Canada R3E 0W3.Received August 4, 1975; accepted for publication March 3, 1976. factors involved in the regulation of myocardial metabolism and function, during infective endocarditis. In the 1950's Olson 3 discussed a hypothetical framework for the study of cardiac metabolism in relat...

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“…By simply adding the appropriate quantity of CaCl2 from a pCa2 stock solution, we obtained the required solutions with pCa 5, 6, and 7. Adequate dilution of pCa 2 stock solution gave pCa 3 tion solutions was confirmed by atomic absorption spectroscopy. In order to mimic the cytoplamatic cation composition, each of the solutions contained, in mM: 140 KCI, 10 NaCI, and 3 MgCl2 according to the reported values about intracellular cation concentrations.…”

Section: Methodsmentioning

confidence: 83%

Restriction by Nitrendipine of Excessive Concentration of Free Intracellular Calcium Ions in Ventricular Myocardium of Hypertensive Rats

et al. 1988

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In earlier investigations it has been found that high arterial blood pressure of salt-sensitive DAHL rats (DAHL-S) that received a diet containing 8% NaCl could be normalized by chronic treatment with specific calcium antagonists, as for instance, nitrendipine or anipamil. Parallel measurements on heart and arterial vasculature with atomic absorption spectrometry revealed that there was a rise in absolute calcium content upon development of hypertension, whereas under the influence of nitrendipine, not only the blood pressure and heart weight but also myocardial (and arterial) tissue calcium content remained in the physiologic range. In the present study, an additional determination of the free intracellular calcium ion concentration with Ca-sensitive microelectrodes was carried out. For technical reasons, the measurements were restricted to isolated resting rat papillary muscles (stretched to optimal length in a perfusion bath of 1.5 ml at 30 degrees C in normal Tyrode solution). The impalement of the electrodes was considered adequate when the heights of Ca potential and membrane potential were constant for more than twenty minutes. In order to produce severe systemic hypertension, a group of six-week-old DAHL-S rats was fed with an 8% NaCl diet over five weeks. Another group of DAHL-S rats received additionally 150 mg/kg nitrendipine twice a day orally. Salt-resistant DAHL-R rats, also fed with an 8% NaCl diet, served as controls. The findings of this preliminary study are as follows (n = 5 in each group): (table; see text).

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Experimental Heart Failure due to Inhibition of Utilisation of High-Energy Phosphates

Cited by 13 publications

References 0 publications

Treatment of verapamil toxicity in intact dogs.

Treatment of verapamil toxicity in intact dogs.

Abnormalities in heart membranes and myofibrils during bacterial infective cardiomyopathy in the rabbit.

Restriction by Nitrendipine of Excessive Concentration of Free Intracellular Calcium Ions in Ventricular Myocardium of Hypertensive Rats

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