Biomedical subjects

S T Wu

Publications and source records attributed to S T Wu.

At least 19 recordsLinked to original sources

PubMed1992

In vitro release of nitroglycerin from topical products by use of artificial membranes.

An in vitro testing method for measuring the release of nitroglycerin from topical drug products was evaluated. The method involved measuring the amount of nitroglycerin that diffused from ointments and patches through various synthetic membranes into receptor fluid contained in a modified Franz diffusion cell. Plots of the amount of nitroglycerin released against the square root of time for all 10 synthetic membranes were linear. Five membranes (group I) were found to release nitroglycerin at similar rates (difference not significant; p > 0.05). Use of the other five membranes (group II) in diffusion cells resulted in release rates significantly slower than those of group I membranes (p < 0.05). Rapid permeation of nitroglycerin from a solution through a polysulfone membrane demonstrated a lack of significant diffusion barrier properties of this membrane. Rates of release of nitroglycerin from commercially available ointments were found to be similar. A comparison of three commercial nitroglycerin patches revealed that these products released nitroglycerin at different rates in vitro.

Administration, Cutaneous↗

PubMed1992

Intracellular calcium during pacing-induced ventricular fibrillation. Effects of lidocaine.

Hemodynamics and endocardial [Ca2+]i transients were studied during ventricular fibrillation in isolated perfused rat hearts. During 1 minute of pacing-induced ventricular fibrillation, the diastolic fibrillatory [Ca2+]i level increased significantly (p less than 0.001) above the end-systolic [Ca2+]i concentration of the last regular contraction. A bolus of lidocaine led to a decrease in the [Ca2+]i level during fibrillation (p less than 0.007) to the end-diastolic level of baseline conditions and then subsequently converted the heart to sinus rhythm. In 13 (62%) of the 21 studies described, post-lidocaine ventricular fibrillation converted to a brief period of asystole followed by sinus rhythm; in 8 (38%) of the studies, post-lidocaine ventricular fibrillation switched to ventricular tachycardia. Postfibrillatory cardiac dysfunction was related to the duration and degree of elevated diastolic [Ca2+]i. The authors conclude that [Ca2+]i levels are increased during ventricular fibrillation, and that lidocaine treatment leads to a prompt decrease in [Ca2+]i preceding conversion to sinus rhythm.

Animals↗

PubMed1992

Relationship between cytosolic calcium and oxygen consumption in isolated rat hearts.

Maximum oxygen consumption was attained in isolated perfused rat hearts using high perfusate calcium and/or isoproterenol, or phenylephrine. The amplitude of calcium transients was directly related to oxygen consumption until oxygen consumed per beat reached maximum. At saturating oxygen consumption the amplitude of [Ca2+]i transients continued to increase, indicative of a calcium overload. In all cases +dP/dt correlated proportionately with +dCa2+/dt. Augmented developed pressure, related to isoproterenol-induced increase in cytosolic cAMP, cannot be attributed totally to elevated levels of [Ca2+]i transients. Adenosine (10(-5) M) added to the medium containing isoproterenol (10(-6) M) negated the isoproterenol-induced increase in cAMP and returned cardiac performance, oxygen consumption, and amplitude of [Ca2+]i transients to control state.

Adenosine Triphosphate↗

PubMed1992

Effects of propafenone on pacing-induced ventricular fibrillation and intracellular calcium in rat hearts.

Propafenone is an antiarrhythmic agent with fast sodium channel, calcium channel, and beta-adrenergic receptor blocking properties. The effects of propafenone on arrhythmias, free intracellular calcium and left ventricular performance were studied using perfused rat hearts during (i) pacing-induced ventricular fibrillation and (ii) infusion with 2.65 x 10(-6) M, 5.3 x 10(-6) M and 7.9 x 10(-6) M propafenone hydrochloride (corresponding to approximately 1, 2 and 3 mg kg-1 body weight). A bolus of 1 mg kg-1 propafenone during ventricular fibrillation resulted in a decrease in intracellular calcium, with subsequent conversion to sinus rhythm. In perfused hearts with sinus rhythm propafenone produced a dose-dependent decrease in heart rate and myocardial oxygen consumption together with a rise in left ventricular diastolic pressure, and diastolic [Ca2+]i, indicative of depression of left ventricular function. We conclude that a bolus of propafenone during ventricular fibrillation leads to a decrease in [Ca2+]i preceding conversion to sinus rhythm. In rat hearts with sinus rhythm the depressive effects of propafenone on [Ca2+]i are dose dependent.

Animals↗

PubMed1991

Angiotensin II and phorbol esters depress cardiac performance and decrease diastolic and systolic [Ca2+]i in isolated perfused rat hearts.

Both angiotensin II and the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), significantly depressed developed pressure, oxygen consumption, and coronary flow in isolated perfused rat hearts and caused a decrease in diastolic and systolic [Ca2+]i and [Ca2+]i transients. PMA and angiotensin II did not change the levels of cAMP but moderately decreased PCr/Cr. The decrease in systolic [Ca2+]i and amplitude of [Ca2+]i transients caused by PMA and angiotensin II resulted in depressed cardiac function. Hearts perfused with PMA and angiotensin II had a decreased sensitivity to extracellular calcium. Depressed developed pressure and oxygen consumption in the PMA- and angiotensin II-treated hearts may have been due to a decrease in amplitude of effective [Ca2+]i transients, because the [Ca2+]i threshold for cross-bridge interaction was presumably higher than the diastolic [Ca2+]i in these hearts.

Angiotensin II↗

PubMed1991

Mechanism for depressed cardiac function in left ventricular volume overload.

To assess the effects of left ventricular chamber volume on the mechanism of changes in left ventricular developed pressure we performed phosphorous-31 nuclear magnetic resonance spectroscopy, hydrogen-1 nuclear magnetic resonance spectroscopy with a shift reagent, two-dimensional echocardiography, atomic absorption spectrophotometry, microsphere analysis, and surface fluorometry on isovolumic isolated perfused rat hearts with incremental intraventricular balloon volumes, while left ventricular pressure was concurrently monitored. A three-phasic response of developed pressure was noted: 0 to 100 microliters balloon volumes resulted in an increase in developed pressure, whereas developed pressure remained constant at 250 microliters and fell at 400 microliters. Oxygen consumption and [Ca2+]i transients followed the same pattern as developed pressure and coronary flow. Intraventricular volumes of 250 microliters or greater (a volume overload) caused endocardial ischemia, a greater decrease in extracellular versus intracellular water, thinning of the left ventricular free wall, and an increase in chamber size. Mechanical pressure on the tissue, induced by the volume overload, caused ischemia as further evidenced by (1) a negative effect on developed pressure, (2) a decrease in [Ca2+]i transients, (3) a [Ca2+]i overload, (4) a moderate decrease in the phosphorylation potential, and (5) an increase in the oxidation-reduction state (nicotinamide-adenine dinucleotide). The high intracellular calcium associated with volume overload may have been due to both compression and ischemia, which leads to an increased number of cross-bridges in rigor, a high end-diastolic pressure, and an increase in wall stress.

Animals↗

PubMed1991

Cardiac function and metabolism after chronic alcohol consumption: adaptation, reversibility, and effects of verapamil.

Hamsters were fed 50% alcohol instead of drinking water for up to 42 weeks (average serum alcohol levels were 0.12 +/- 0.06 gm/dl during the 42 weeks). One group of hamsters (28 weeks) was given verapamil 3 days before they were killed. Two groups were withdrawn from alcohol acutely (3 days before they were killed) at 14 and 28 weeks. High-energy phosphate compounds were studied in isolated hearts with 31P-MRS standardized by freeze clamping the tissue. Hemodynamics of the heart were monitored throughout the study. After 7 and 14 weeks of alcohol ingestion, developed pressure and the phosphorylation potential were depressed in the hearts of chronically treated hamsters. At 28 and 42 weeks developed pressure increased but was significantly below baseline values; however, the phosphorylation potential and [pH]i returned to baseline values at 28 and 42 weeks. Throughout the 7 to 42 weeks of alcohol ingestion the alcohol-treated hamsters had a significantly higher end-diastolic pressure as compared with control animals. Withdrawal of alcohol (3 days before the hamsters were killed) reversed the depression of developed pressure and the phosphorylation potential. Acute administration of verapamil (therapeutic dose 3 days before they were killed) to hamsters given alcohol for 28 weeks reversed the depressed hemodynamic values. Overall the data suggest an adaptation of the heart to continuing alcohol consumption, which was related to normalization of the phosphorylation potential and [pH]i and partial alleviation of functional depression.

Alcoholism↗

PubMed1991

Intracellular endocardial calcium and myocardial function in rat hearts.

Analyses of [Ca2+]i in the isolated beating rat heart (using Indo-1 dye) demonstrated a direct relationship between developed pressure and each of the following: (a) systolic [Ca2+]i; (b) amplitude of [Ca2+]i transients; and (c) diastolic level of [Ca2+]i. Agents which increased cAMP levels, augmented amplitude of [Ca2+]i transients, and lowered the resting level of [Ca2+]i, thereby shifting the relationship between developed pressure and diastolic as well as systolic [Ca2+]i concentrations towards lower [Ca2+]i levels for comparable peak systolic pressure measurements at constant end-diastolic pressure. Addition of adenosine to the perfusate containing isoproterenol completely prevented any cAMP-induced cytosolic changes. Interventions which altered [Ca2+]i and developed pressure, but did not increase cAMP (e.g., perfusion pressure, extracellular calcium, calcium entry blockers, and alpha agonist), caused an increase in diastolic levels of [Ca2+]i commensurate with the augmentation in developed pressure and amplitude of [Ca2+]i transients. When the diastolic [Ca2+]i rose to 400 nmoles and the cAMP was below 4 nmoles the heart fibrillated. The heart fibrillated at a diastolic [Ca2+]i of 350 nmoles when the cAMP was elevated to 6 nmoles. The diastolic level of [Ca2+]i at which the heart begins to fibrillate is indicative of the effect contraction threshold.

Adenosine↗

PubMed1991

[Ca2+]i transients in the cardiomyopathic hamster heart.

Intracellular [Ca2+] transients were studied in isolated hearts of healthy and cardiomyopathic hamsters in late failure perfused with glucose or pyruvate. Hearts of healthy hamsters developed similar pressures when perfused with either glucose or pyruvate, and [Ca2+]i transients were comparable in amplitude when perfused with either substrate. On the other hand, hearts of cardiomyopathic hamsters in late failure developed normal pressure when perfused with pyruvate but developed depressed pressure (50%) when perfused with glucose. The amplitude of [Ca2+]i transients fell severely and was associated with a high diastolic [Ca2+]i in cardiomyopathic hamster hearts when the perfusate was switched from pyruvate to glucose. The high phosphomonoester sugars as evidenced by 31P nuclear magnetic resonance studies and the depressed oxygen consumption in the cardiomyopathic hamster hearts perfused with glucose reflect an inhibition in glycolysis and a subsequent decrease in mitochondrial activity. Without an adequate delivery of substrate to the mitochondria in the cardiomyopathic hamster, the myocardium is no longer capable of maintaining its [Ca2+]i homeostasis.

Animals↗

PubMed1990

Calcium-dependent fluorescence transients during ventricular fibrillation.

Using surface fluorometry, calcium-dependent fluorescence transients were recorded during ventricular fibrillation in perfused rat and hamster hearts loaded with INDO 1-AM (fluorimetric reagent for calcium ion). Among a series of 203 consecutive isolated heart studies, 13 instances of ventricular fibrillation occurred. These arrhythmias developed during pretreatment with isoproterenol, dobutamine, norepinephrine, phenylephrine, digoxin, and 4 mmol/L calcium in the perfusate. Alternans behavior of calcium transients occurred in three cases; premature beats preceded ventricular fibrillation in six cases. Premature beats led to a further increase in the free intracellular calcium ([Ca2+]i) concentration, resulting in a stronger contraction with the subsequent beat and/or the initiation of ventricular fibrillation. Two distinct patterns of calcium transients were seen: ventricular fibrillation type 1 showed fast disorganized transients with small amplitude and an irregular, nonuniform tracing; type 2 revealed fast activity and multiform, polymorphous transients with marked changes in amplitude. Independent of the morphologic type of fibrillation, [Ca2+]i remained constant or even increased during an observation time up to 9 minutes. No intracellular hypocalcemia was observed. Isoproterenol pretreatment resulted in [Ca2+]i levels in the range of the end-diastolic calcium level of the last regular contraction. Fibrillating calcium transients after norepinephrine, dobutamine, phenylephrine, digoxin, high calcium, and fast pacing were in the previous end-systolic range. It is suggested that inotropic agents acting without a major elevation of cyclic adenosine monophosphate result in higher [Ca2+]i.

Animals↗

PubMed1990

31P magnetic resonance spectroscopy of pressure overload hypertrophy in rats: effect of reduced perfusion pressure.

STUDY OBJECTIVE - The purpose of the study was to confirm the presence of abnormalities in the coronary vessels of hypertensive hearts, and to examine the effects of reduced coronary perfusion pressure. DESIGN - Rats were made hypertensive by aortic banding, after which coronary flow and myocardial energy metabolites were studied in isolated hearts at physiological (140 cm H2O) and reduced (80 cm H2O) coronary perfusion pressures and compared with normotensive controls. SUBJECTS - Wistar-Kyoto rats between 250 and 300 g were used. Left ventricular hypertrophy was generated by aortic banding in 29 rats; 8 were studied one week after banding, and 21 three weeks after banding. There were 45 controls. MEASUREMENTS and RESULTS - Energy metabolites were assessed using 31P magnetic resonance spectroscopy, standardised by high performance liquid chromatography of rapidly freeze clamped tissue. Left ventricular wall thickness was determined using two dimensional echocardiography. Coronary flow (normalised for heart weight) was reduced significantly after one and three weeks of left ventricular hypertrophy, and at either physiological or below physiological pressures. Hearts from aortic banded animals developed higher intraventricular pressure with reduced oxygen consumption when perfused at a physiological pressure, indicating increased thermodynamic efficiency. When perfused at reduced pressure, the developed pressure declined significantly in both the one week and the three week banded groups compared to normal hearts. The phosphorylation potential and intracellular pH (pHi) were not significantly lower after one week and three weeks of left ventricular hypertrophy when perfused at physiological pressure. When perfused at reduced pressure, phosphorylation potential declined significantly in both groups of hypertrophied hearts, whereas pHi declined significantly only in the three week hypertrophy group. CONCLUSIONS - There is improved thermodynamic efficiency of the hypertrophied myocardium when perfused at a physiological pressure, but when perfused at a reduced pressure, ventricular function, phosphorylation potential and pHi decline in rat hearts after three weeks of aortic constriction, indicating an impairment of coronary reserve.

Animals↗

PubMed1990

Postischemic recovery of mechanical performance and energy metabolism in the presence of left ventricular hypertrophy. A 31P-MRS study.

The present study was undertaken to define the effects of left ventricular hypertrophy on postischemic recovery of myocardial performance and high energy phosphate metabolism. Hemodynamics and 31P-magnetic resonance spectra were monitored simultaneously in the isolated Langendorff-perfused rat heart during 30 minutes of ischemia and 30 minutes of reperfusion. Left ventricular hypertrophy was produced by either suprarenal aortic constriction or chronic thyroxine administration. In chronic pressure overload hypertrophy, minimal coronary resistance was significantly higher (p less than 0.001) and the loss of purine nucleosides in the coronary effluent during early reperfusion significantly larger (p less than 0.001) compared with both normal hearts and thyroxine-induced hypertrophied hearts. Postischemic recovery of the baseline values for left ventricular developed pressure and phosphorylation potential was 43 +/- 4% and 82 +/- 4%, respectively, in chronic pressure overload hypertrophied hearts; 86 +/- 4% and 91 +/- 3%, respectively, in normal hearts (chronic pressure overload hypertrophy versus normal hearts, p less than 0.001 and p less than 0.05); and 100 +/- 4% and 98 +/- 2%, respectively, in thyroxine-induced hypertrophied hearts (normal hearts versus thyroxine-induced hypertrophied hearts, p less than 0.05 and p less than 0.05). Recovery after reperfusion was not related to intracellular pH, ATP, phosphocreatine, or inorganic phosphate levels during ischemia. Also, recovery was not related to developed pressure or oxygen consumption before ischemia. However, recovery was inversely related to coronary resistance and directly related to coronary flow before ischemia. Thus, functional and/or anatomic alterations of the coronary vascular bed and a greater loss of purine nucleosides during reperfusion are likely responsible for the attenuated compensatory response to ischemia and reperfusion in left ventricular hypertrophy induced by chronic pressure overload. On the other hand, the excess muscle mass per se does not seem to alter recovery, since thyroxine-induced myocardial hypertrophied hearts responded at least as well as normal hearts.

Animals↗

PubMed1990

Dobutamine potentiates amrinone's beneficial effects in moderate but not in advanced heart failure. 31P-MRS in isolated hamster hearts.

There is controversy as to whether potent inotropic agents are beneficial or detrimental in moderate to severe heart failure. Accordingly, we studied the effects of amrinone, amrinone plus dobutamine, and dobutamine alone on mechanical performance, myocardial oxygen consumption, and high energy phosphate metabolism in different stages of congestive heart failure in the cardiomyopathic Syrian hamster. In hearts with moderate heart failure, administration of amrinone, amrinone plus dobutamine, and dobutamine alone increased developed pressure significantly, whereas the phosphorylation potential increased significantly only with amrinone and amrinone plus dobutamine. In hearts with advanced heart failure, administration of amrinone and amrinone plus dobutamine increased developed pressure significantly, whereas dobutamine alone had no effect. The phosphorylation potential improved significantly only with amrinone. Thus, amrinone improved mechanical performance and mitochondrial activity in both heart failure states. Dobutamine potentiated amrinone's beneficial effects in moderate heart failure, but negated the positive inotropic effect of amrinone in advanced heart failure. Therefore, hearts responded differently to potent inotropic agents depending on the severity of heart failure.

Amrinone↗

PubMed1989

Influence of positive inotropic agents on intracellular calcium transients. Part I. Normal rat heart.

This study, which was designed to evaluate the effects of positive inotropic agents on intracellular calcium transients ([Ca2+]i), is the first to analyze calcium transients in the whole heart. The positive inotropic agents that augment intracellular cyclic adenosine monophosphate (cAMP) (dibutyryl cAMP, amrinone, and isoproterenol) caused an increase in developed pressure and [Ca2+]i transients and a decrease in diastolic [Ca2+]i. On the other hand, the glycoside digoxin and the alpha-adrenoceptor agents, phenylephrine and dobutamine, also caused an increase in [Ca2+]i transients and developed pressure. However, unlike the agents that increase [cAMP]i, they induced an elevation in diastolic [Ca2+]i. With all the positive inotropic agents, developed pressure increased commensurately with the percentage changes in amplitude of the [Ca2+]i transients.

Animals↗

PubMed1989

Influence of positive inotropic agents on intracellular calcium transients. Part II. Cardiomyopathic hamster hearts.

To study the mechanism of dobutamine on end-stage heart failure, we assessed hemodynamic responses, high-energy phosphates (31P-NMR), and free intracellular calcium ([Ca2+]i) transients (surface fluorometry) during perfusion with 10(-6) mol/L dobutamine in Syrian cardiomyopathic hamsters with severe heart failure. These results were compared to perfusion of the heart with 10(-6) mol/L norepinephrine and 10(-6) mol/L isoproterenol. With the positive inotropic agents the rate-pressure product increased immediately (p less than 0.01 with dobutamine, norepinephrine; p less than 0.003 with isoproterenol); after 10 to 15 minutes of perfusion the rate-pressure product remained relatively stable with norepinephrine and isoproterenol but decreased with dobutamine (p = NS vs control values). [Ca2+]i-transients increased significantly in all groups. The end-diastolic [Ca2+]i decreased continuously with norepinephrine and isoproterenol (p less than 0.008; p less than 0.005) but increased during dobutamine by 19%. Alterations in coronary flow, pHi, high-energy phosphates, and the phosphorylation potential were not significantly different among the three catecholamines. In conclusion, in contrast to norepinephrine and isoproterenol, dobutamine depressed myocardial performance and increased end-diastolic [Ca2+]i in late heart failure.

Animals↗

PubMed1989

The effect of dobutamine on myocardial performance and high-energy phosphate metabolism at different stages of heart failure in cardiomyopathic hamsters: a 31P MRS study.

Dobutamine has been shown to exert disparate clinical effects in patients with cardiomyopathy and heart failure. This study evaluated the effects of dobutamine on hemodynamics and energetics in isolated, perfused myopathic hamster hearts at a moderate and advanced stage of heart failure. Biochemical changes were correlated with left ventricular developed pressure, coronary flow, and myocardial oxygen consumption. During dobutamine treatment left ventricular developed pressure increased in the control and moderate heart failure group 28.0 +/- 1.0% and 114.2 +/- 11.6%, respectively. Myocardial oxygen consumption increased 50.1 +/- 9.1% and 45.5 +/- 16.0%, respectively. There were no significant changes of left ventricular developed pressure and myocardial oxygen consumption in the advanced heart failure group. Inorganic phosphate (Pi) increased in the control group from 6.8 +/- 0.5 to 11.4 +/- 1.2 mmol (p less than 0.005) and in the advanced heart failure group from 10.4 +/- 1.1 to 15.3 +/- 1.2 mmol (p less than 0.01). Phosphocreatine (PCr) and beta-ATP (adenosine triphosphate) decreased in the control group from 12.2 +/- 0.4 to 8.7 +/- 0.7 mmol (p less than 0.001) and 10.4 +/- 0.8 to 7.7 +/- 0.7 mmol (p less than 0.02), respectively. PCr/Pi ratio, reflecting mitochondrial function, fell in the control and advanced heart failure group from 1.84 +/- 0.14 to 0.84 +/- 0.14 (p less than 0.02) and 0.81 +/- 0.16 to 0.37 +/- 0.08 (p less than 0.03), respectively. Thus in cardiomyopathic hamsters dobutamine improved mechanical performance and thermodynamic efficiency in moderate stages of heart failure by improving mitochondrial activity, but did not improve mechanical performance in an advanced stage of heart failure. These experiments provide into the disparate clinical effects of dobutamine at various stages of heart failure.

Adenosine Triphosphate↗

PubMed1989

Verapamil preserves myocardial performance and energy metabolism in left ventricular hypertrophy following ischemia and reperfusion. Phosphorus 31 magnetic resonance spectroscopy study.

While calcium entry blockers have a beneficial influence on the postischemic recovery of the nonhypertrophied heart, their influence on the hypertrophied heart has not been determined. The aim of this study was to assess postischemic recovery of myocardial performance and energy metabolites in rat hearts with left ventricular hypertrophy pretreated either chronically or acutely with verapamil. Left ventricular hypertrophy was induced by suprarenal constriction of the abdominal aorta. Hemodynamics and phosphorus 31 magnetic resonance spectra were monitored simultaneously in the isolated hearts during control perfusion, after 30 minutes of global ischemia, and after 30 minutes of reperfusion. All hypertrophied hearts had significantly higher rate-pressure products than normal hearts. Compared with normal hearts, oxygen consumption was significantly lower in all hypertrophied hearts, especially untreated hypertrophied hearts. Also, before ischemia all normal or hypertrophied hearts (treated or untreated) began with comparable phosphorylation potentials (i.e., the supply of energy was not significantly different). Postischemic recovery was not related to energy supply-oxygen demand before onset of ischemia. Furthermore, it was not related to energy levels or intracellular pH during ischemia. For postischemic recovery, the rate-pressure product was 40 +/- 5% in the hypertrophied heart, 83 +/- 5% in the normal, 100 +/- 3% in the hypertrophied heart chronically treated with verapamil, and 82 +/- 5% in the hypertrophied heart acutely treated with verapamil. The degree of recovery was related to coronary flow both before and after ischemia. The latter is important for flushing deleterious metabolites and ions from the interstitial space as well as for delivery of oxygen and substrate to the myocardium.

Adenosine Triphosphate↗

PubMed1988

Hydrodynamics in the heart modulates work.

The hydrostatic pressure (perfusion pressure) of the isovolumic isolated perfused rat heart regulated the hydrodynamics (water movement) of the myocardium. An abrupt (10 s) decrease in hydrostatic pressure caused an immediate decrease in oxygen consumption, left ventricular developed pressure, and wall thickness. Wall thickness was determined by two-dimensional echocardiography. When the perfusion pressure was again returned to the control values (140 cm H2O) oxygen consumption, developed pressure, and wall thickness returned to control values within 10-30 s. An abrupt decrease in perfusion pressure also caused an immediate decrease in both extracellular and intracellular water in the heart as determined by H-1 NMR (nuclear magnetic resonance) with the shift reagent Dy(TTHA)3- (Dysprosium triethylene tetramine-hexaacetate). Similar findings were obtained using K(CoEDTA) (potassium cobalt ethylenediaminetetraacetate) utilized as an extracellular marker. With a decrease in intracellular water in the heart, there was a concurrent decrease in intracellular calcium.

Animals↗