Influence of glucose metabolism on ouabain-induced changes in the transmembrane potential and contraction of human heart in vitro

1970 ◽  
Vol 48 (12) ◽  
pp. 801-812 ◽  
Author(s):  
K. Prasad ◽  
John C. Callaghan

Effects of glucose, anoxia, iodoacetate, and 2,4-dinitrophenol on the ouabin-induced changes in the simultaneously recorded transmembrane action potential and contraction of 72 human papillary muscle strips obtained from 36 patients undergoing corrective open heart surgery were investigated. Ouabain (10−8M, 10−9M, 10−10M) produced a shortening of the action potential duration (APD) and an increase in the force of contraction in the muscle. Non-oxygenated glucose-free solution, iodoacetate (10−5M), and 2,4-dinitrophenol (10−6M) produced partial to complete inhibition of the positive inotropic effects of ouabain (10−8M or 10−9M) in the papillary muscles. The shortening of the APD produced by ouabain was further enhanced in the presence of the above metabolic inhibitors. As the glucose level was raised (0, 5, 10, 20, 30 mM), anoxic papillary muscles responded to ouabain by a progressive increase in the force of contraction and a parallel increase in the APD. Glucose (30 mM) was effective in restoring the positive inotropic effects of ouabain in DNP-poisoned muscle while it was ineffective in doing so in the muscle poisoned with both IAA and DNP. These results indicate the requirement of energy for the positive inotropic effects of ouabain in cardiac muscle.

1970 ◽  
Vol 48 (4) ◽  
pp. 241-253 ◽  
Author(s):  
K. Prasad

The effects of changes in extracellular concentrations (25, 50, 100, 140 mM) of NaCl on the simultaneously recorded action potential (AP) and contraction of guinea pig papillary muscle in the presence of various concentrations of glucose (0, 5, 20, 30, 50 mM) and CaCl2 (0, 0.5, 1.0, 2.5 mM) were investigated. Low sodium (25 mM) produced a marked shortening of the action potential duration (APD) associated with a marked increase in the force of contraction but a small change in AP amplitude. A direct relation between extracellular NaCl and cardiac contraction was observed. There was no relation between AP amplitude and cardiac contraction. Low sodium induced shortening of the APD was greater in the absence of glucose than in its presence while the increase in the force contraction induced by low Na was markedly reduced in the absence of glucose. Low sodium was practically ineffective in restoring the contraction of papillary muscle in the absence of CaCl2. A calcium concentration dependent increase in the force of contraction was associated with a corresponding shortening of the APD in low sodium. Anoxia markedly reduced the positive inotropic effects of low sodium and enhanced the low sodium induced shortening of the APD in the papillary muscle. Glucose produced a marked lengthening of the APD which was shortened during anoxia but it was effective only slightly in lengthening the APD shortened by low sodium. The effects of ouabain in the muscles in the presence of low sodium were reduced. It is suggested that the changes in the APD accompanied by changes in the contraction in the guinea pig papillary muscle might be associated with NaCl-induced changes in the membrane ATPase. The low sodium induced increase in the force of contraction seems to be dependent upon both calcium and energy supply.


2011 ◽  
Vol 111 (3) ◽  
pp. 799-807 ◽  
Author(s):  
Justin T. Sambol ◽  
Marlon A. Lee ◽  
Mingshan Jiang ◽  
Garima Dosi ◽  
Wei Dong ◽  
...  

Myocardial contractile dysfunction develops following trauma-hemorrhagic shock (T/HS). We have previously shown that, in a rat fixed pressure model of T/HS (mean arterial pressure of 30–35 mmHg for 90 min), mesenteric lymph duct ligation before T/HS prevented T/HS-induced myocardial contractile depression. To determine whether T/HS lymph directly alters myocardial contractility, we examined the functional effects of physiologically relevant concentrations of mesenteric lymph collected from rats undergoing trauma-sham shock (T/SS) or T/HS on both isolated cardiac myocytes and Langendorff-perfused whole hearts. Acute application of T/HS lymph (0.1–2%), but not T/SS lymph, induced dual inotropic effects on myocytes with an immediate increase in the amplitude of cell shortening (1.4 ± 0.1-fold) followed by a complete block of contraction. Similarly, T/HS lymph caused dual, positive and negative effects on cellular Ca2+ transients. These effects were associated with changes in the electrophysiological properties of cardiac myocytes; T/HS lymph initially prolonged the action potential duration (action potential duration at 90% repolarization, 3.3 ± 0.4-fold), and this was followed by a decrease in the plateau potential and membrane depolarization. Furthermore, intravenous infusion of T/HS lymph, but not T/SS lymph, caused myocardial contractile dysfunction at 24 h after injection, which mimicked actual T/HS-induced changes; left ventricular developed pressure (LVDP) and the maximal rate of LVDP rise and fall (±dP/d tmax) were decreased and inotropic response to Ca2+ was blunted. However, the contractile responsiveness to β-adrenergic receptor stimulation in the T/HS lymph-infused hearts remained unchanged. These results suggest that T/HS lymph directly causes negative inotropic effects on the myocardium and that T/HS lymph-induced changes in myocyte function are likely to contribute to the development of T/HS-induced myocardial dysfunction.


1992 ◽  
Vol 58 ◽  
pp. 271
Author(s):  
Michio Yajima ◽  
Yoshihiro Hotta ◽  
Pao Chi Isao ◽  
Hiroaki Ando ◽  
Hirohiko Nomura ◽  
...  

Perfusion ◽  
1986 ◽  
Vol 1 (2) ◽  
pp. 99-102
Author(s):  
B. Touchot ◽  
F. Laborde ◽  
F. Dum ◽  
P. Commin ◽  
P. Gallix ◽  
...  

Cardiopulmonary bypass (CPB) standard heparin and protamine therapy is a relatively satisfactory part of conventional CPB practice. However, some problems are known to result from both heparin and protamine sulphate administration. These include: allergic reaction and thrombocytopenia due to heparin, and anaphylactoid reactions, negative inotropic effects, pulmonary oedema and pulmonary hypertension due to protamine administration. Low molecular weight heparin (LMWH) should theoretically be superior decreasing the adverse effects of standard heparin. In addition, it should not require the use of protamine for heparin neutralization. These potential benefits of LMWH encourage the experimental evaluation of the use of LMWH during open-heart surgery before preliminary clinical applications.


1995 ◽  
Vol 268 (5) ◽  
pp. H1838-H1846 ◽  
Author(s):  
M. M. Doohan ◽  
L. C. Hool ◽  
H. H. Rasmussen

Thyroid status influences the abundance of Na(+)-K+ pumps in the heart. To evaluate whether this phenomenon may contribute to a dependence of the action potential duration (APD) on thyroid status, we induced hypothyroidism in a group of New Zealand White rabbits. Another group was treated similarly but also received triiodothyronine (T3). Right ventricular myocytes were isolated and voltage clamped at -40 mV. We identified Na(+)-K+ pump current (Ipump) as a ouabain-induced shift in holding current. Mean Ipump, measured using patch pipettes containing 10 mM Na+, was 0.24 +/- 0.02 pA/pF in 9 cells from 4 hypothyroid rabbits and 0.48 +/- 0.05 in 10 cells from 4 rabbits treated with T3 (P < 0.001). Because thyroid status influences Na+ influx, we measured intracellular Na+ activity (aiNa) in right ventricular papillary muscles. We found that aiNa was 5.20 +/- 0.42 mM in nine papillary muscles from seven hypothyroid rabbits and 7.62 +/- 0.69 mM in nine papillary muscles from six rabbits treated with T3 (P < 0.01). The effect of thyroid-induced changes in Ipump and aiNa on APD was stimulated with a computer model. The simulations predicted that thyroid-induced changes in Ipump can influence APD. The predicted changes were similar to changes in APD measured in isolated papillary muscles.


1965 ◽  
Vol 48 (5) ◽  
pp. 887-899 ◽  
Author(s):  
Don P. MacLeod ◽  
E. E. Daniel

The response of the cat papillary muscle to anoxia has been found to alter depending on the glucose concentration in the medium. At a glucose concentration of 5 mM anoxia caused a marked reduction in force of contraction and action potential duration within 20 minutes. At a glucose concentration of 50 mM anoxia induced similar changes in the force of contraction but little or no change in action potential duration. Elevation of glucose concentration during an anoxic interval reversed the anoxia-induced changes in action potential but had little effect on force of contraction. This effect of glucose could be partially duplicated by xylose and 2-deoxyglucose and in addition, 2-deoxyglucose has been found to prevent the effect of subsequently added glucose. These sugars appear to be transported by a system responsible for glucose transport but are not metabolized to any extent. It would appear therefore that transport of glucose is in some way related to transport of potassium as increased potassium permeability is thought by many to be responsible for anoxia-induced changes in action potential duration.


Sign in / Sign up

Export Citation Format

Share Document