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S M Krause

Publications and source records attributed to S M Krause.

At least 19 recordsLinked to original sources
PubMed1998

Lack of beneficial effects of growth hormone treatment in conscious dogs during development of heart failure.

The effects of chronic treatment with growth hormone (porcine GH, 0.56 mg.kg-1.day-1 s.c.) were examined in dogs with heart failure induced by rapid ventricular pacing (240 beats/min) for 4 wk. Fourteen conscious dogs were studied 2-3 wk after surgical instrumentation with catheters in the descending aorta and left atrium, a pressure gauge in the left ventricle (LV), a flow probe around the ascending aorta, pacing leads on the ventricular free wall and left atrium, and ultrasonic crystals on the opposing anterior and posterior endomyocardium of the LV. GH treatment for 4 wk significantly increased both body weight and plasma insulin-like growth factor 1 (IGF-1) compared with vehicle-treated dogs (P < 0.01, +2.0 +/- 0.5 vs. +0.3 +/- 1.1 kg; 1,043 +/- 218 vs. 241 +/- 64 ng/ml, respectively). However, the changes in resting LV systolic (i.e., both isovolumic and ejection phases) and diastolic function (i.e., isovolumic relaxation time constant tau) and the systemic vascular resistance were similar for the GH- and vehicle-treated groups during the development of heart failure. LV contractile reserve, assessed with step infusion of isoproterenol or dobutamine challenge, was markedly attenuated after heart failure, but there were no differences between the GH- and vehicle-treated groups. During the progression of heart failure, the increases in plasma atrial natriuretic peptide correlated (P < 0.01) directly with left atrial pressure and inversely with LV circumferential fiber shortening. However, GH treatment did not substantially modify these relationships. In addition, renal function and myocardial ultrastructure at the advanced stage of heart failure also showed similar changes for the GH- and vehicle-treated groups. We conclude that in conscious dogs during the development of congestive heart failure produced by rapid ventricular pacing, GH at a dose that increases body weight and plasma IGF-1 levels does not affect LV performance or systemic vascular dynamics.

Adrenergic beta-Agonists↗
PubMed1997

Renal protection by a dual ETA/ETB endothelin antagonist, L-754,142, after aortic cross-clamping in the dog.

Renal insufficiency is a significant complication that occurs after surgical procedures, requiring cross-clamping of the aorta. The mechanism for this renal dysfunction is currently not known, but studies suggest a potential role of endothelin in mediating the insufficiency. Accordingly, the role of endothelin was assessed using the nonpeptidyl, dual ETA/ETB endothelin antagonist L-754,142 in a model of renal insufficiency in the anesthetized dog induced by cross-clamping the suprarenal aorta for 60 min, followed by 2 h of reperfusion. In vehicle-treated animals (saline, n = 8) after 2 h of reperfusion, plasma [ET-1] increased 66% and renal blood flow (RBF) was reduced by 38% compared with baseline. This decline was associated with an 84% increase in renal vascular resistance and a 54% reduction in GFR (baseline, 46 +/- 5 ml/min; 21 +/- 3 ml/min at 2 h; P < 0.01) and sodium reabsorption (baseline, 6.7 +/- 0.7 microEq/min; 3.0 +/- 0.5 microEq/min at 2 h, P < 0.01). After baseline measurements, pretreatment with L-754,142 at 0.3 mg/kg bolus + 0.1 mg/kg per h continuous infusion (low dose; n = 8) or 3.0 mg/kg bolus + 1 mg/kg per h infusion (high dose; n = 8) initiated 45 min before aortic cross-clamp led to a dose-dependent normalization of RBF and renal vascular resistance within 2 h of cross-clamp removal. GFR was also improved and returned to within 75% of baseline (P < 0.01 versus vehicle) by 2 h of reperfusion with L-754,142 (baseline, 55 +/- 5 ml/min; 42 +/- 5 ml/min at 2 h with the high dose). The improvement of GFR with L-754,142 treatment was associated with a preservation of sodium reabsorption compared with vehicle-treated animals. This study supports a role of endothelin in the pathogenesis of renal insufficiency after aortic cross-clamping and demonstrates that pretreatment with the dual ETA/ETB endothelin antagonist L-754,142 preserves RBF and sodium reabsorption, leading to a significant improvement in GFR.

Acetamides↗
PubMed1996

Pharmacology of L-744,453, a novel nonpeptidyl endothelin antagonist.

L-744,453 ((+/-)3-[4-(1-carboxy-1-(3,4-methylenedioxyphenyl)methoxy)-3,5-diprop ylphenyl methyl]-3H-imidazo[4,5-c]pyridine) is an endothelin (ET) receptor antagonist from a new structural class, the dipropyl-alpha-phenoxyphenylacetic acid derivatives. L-744,453 competitively and reversibly inhibits [125I]-ET-1 binding to Chinese Hamster Ovary cells expressing cloned human ET receptors (K(i)s: hET(A)=4.3 nM; hET(B)=232 nM), and is selective for endothelin receptors compared to other peptide receptors. It is an antagonist of ET-1 stimulated phosphatidyl inositol hydrolysis in rat uterine slices (IC50=220 nM) and exhibits no agonist activity. This compound also inhibits ET-1 stimulated contraction of rat aortic rings with a K(b) value of 50 nM. L-744,453 protects against ET-1 induced lethality in mice after i.v. (AD50=13 mg/kg i.v.) or oral administration. This compound also antagonizes ET-1 induced increases in diastolic blood pressure in conscious normotensive rats (AD50=0.67 mg/kg i.v.) and anesthetized ferrets (AD50=1.6 mg/kg i.v.). L-744,453 is a potent, selective, orally active endothelin antagonist which may be useful in elucidating the role of endothelin in normal and pathophysiological states.

Animals↗
PubMed1995

Pharmacology of L-754,142, a highly potent, orally active, nonpeptidyl endothelin antagonist.

L-754,142, (-)-N-(4-iso-propylbenzenesulfonyl)-alpha-(4-carboxyl-2-n-propy lphenoxy)-3,4- methylenedioxyphenylacetamide, is a potent nonpeptidyl endothelin antagonist (e.g., Ki: cloned human ETA = 0.062 nM: cloned human ETB = 2.25 nM), with high specificity for endothelin receptors. In vitro, L-754,142 is a potent antagonist of ET-1-induced phosphatidyl inositol hydrolysis in Chinese hamster ovary cells expressing cloned human endothelin receptors (IC50: hETA = 0.35 nM; hETB = 26 nM) and of ET-1 induced contractions in rabbit iliac artery rings (pA2 = 7.74) and rat aortic rings (pA2 = 8.7). In vivo, L-754,142 is a potent and specific antagonist of exogenously administered ET-1 or big ET-1, L-754,142 fully protects against ET-1-induced lethality in mice (AD50 = 0.26 mg/kg i.v.). The pressor response to big ET-1 in the anesthetized ferret is blocked by this compound with an ED50 value of 0.019 mg/kg i.v. L-754,142 also blocks the pressor response to big ET-1 in the conscious rat with ED50 values of 0.30 mg/kg i.v. and 0.56 mg/kg p.o. The duration of action of L-754,142 in this rat model is more than 12 hr after an oral dose of 3 mg/kg. In summary, L-754,142 is a potent, orally active ET antagonist with a long duration of action in several in vivo models.

Acetamides↗
PubMed1994

Intravenous administration of the endothelin-1 antagonist BQ-123 does not ameliorate myocardial ischaemic injury following acute coronary artery occlusion in the dog.

OBJECTIVE: It has been proposed that myocardial ischaemic injury is modulated in part by the release of endothelin-1 from the coronary endothelium either during ischaemia or following reperfusion. Release of sufficient amounts of endothelin-1 would result in coronary vasoconstriction and could potentiate ischaemic damage. An endothelin-1 antagonist, BQ-123, was given intravenously to evaluate the role of endothelin-1 in postischaemic injury and determine whether blockade of the ETA receptor would afford protection from ischaemia/reperfusion injury. METHODS: Myocardial injury was induced in anaesthetised dogs using 90 min of left circumflex coronary artery occlusion followed by 4 h of reperfusion. Animals treated with a continuous intravenous infusion of BQ-123 (0.1 mg.kg-1.min-1), begun 10 min before ischaemia and continued throughout ischaemia and reperfusion, were compared to saline treated animals. RESULTS: After 4 h of reperfusion the myocardial infarct size measured by triphenyltetrazolium chloride staining was not different between the two groups. Infarct size in the control group was 25.7 (SEM 5.4)% of the area at risk while BQ-123 treatment resulted in an infarct size of 29.2(7.1)% of the area at risk (p = 0.70). Plasma endothelin-1 concentration measured at the coronary sinus was only significantly increased following 5 min of reperfusion. CONCLUSIONS: The intravenous administration of a specific ETA receptor antagonist does not protect against ischaemia/reperfusion injury. These results suggest that endothelin-1 receptor antagonists require access to the area at risk during occlusion to protect the myocardium from ischaemic injury.

Animals↗
PubMed1992

Specific enhancement of the cardiac myofibrillar ATPase by bound creatine kinase.

The kinetic influence of bound creatine kinase (CK) on the Ca(2+)-activated myosin ATPase was evaluated. ATPase rates were measured from 0.8 microM to 3.2 mM MgATP. Under control conditions, the apparent KmATP was 79.9 +/- 13.3 microM. In contrast, the addition of 12.2 mM phosphocreatine (PCr) decreased the apparent KmATP to a value of 13.6 +/- 1.4 microM. To determine if this reduction was merely the result of an ATP maintenance system, ATP was regenerated using either phosphoenolpyruvate and pyruvate kinase (PEP-PK), or PCr and soluble bovine cardiac CK. Data obtained with PEP + PK indicated an apparent KmATP of 65.5 +/- 7.3 microM. To study the effects of exogenous CK, the endogenous CK was irreversibly inhibited with 1 mM iodoacetamide. The kinetics of the ATPase were then examined by adding soluble CK to the incubation medium. Under these conditions, the KmATP was 56.4 +/- 0.86 microM. Therefore, these two ATP regeneration systems could not duplicate the effects of endogenous CK. The reduction of the apparent KmATP by endogenous CK was not the result of an altered inhibition by MgADP. MgADP inhibition was determined to be non-competitive, with a Ki of 5.0 +/- 0.1 mM. These data suggest that the observed kinetic effects reflect the proximity of the enzymes in the myofibrillar bundle, thus emphasizing the importance of bound CK for the localized regeneration of MgATP utilized by the myosin ATPase.

Adenosine Diphosphate↗
PubMed1991

Effect of increased free [Mg2+]i with myocardial stunning on sarcoplasmic reticulum Ca(2+)-ATPase activity.

Intracellular free Mg2+ concentration [( Mg2+]i) has been shown to increase markedly during ischemia from 0.6 to 3.2 mM and remain elevated severalfold at 1.5 mM after reperfusion of the stunned heart. The significance of this rise in [Mg2+]i after reperfusion on cellular function is not well known. To determine whether this increase in free [Mg2+] would alter the function of the sarcoplasmic reticulum (SR), the effects of an increase in free [Mg2+] on the SR Ca(2+)-dependent Mg(2+)-adenosinetriphosphatase (ATPase) activity were examined in SR isolated from Langendorff-perfused, isovolumic rabbit hearts after 15 min of reversible ischemia (global stunning). Oxalate-supported Ca2+ transport, assessed under identical conditions (0.4 mM free Mg2+, 15 microM free Ca2+), was reduced from 495 +/- 29 to 395 +/- 27 nmol Ca2+.mg protein-1.min-1 in control and stunned hearts, respectively, indicating a defect in enzyme function. This defect was confirmed by a decrease in the maximal Ca(2+)-dependent Mg(2+)-ATPase activity. An increase in the free [Mg2+] to simulate conditions after reperfusion leads to a decrease in the Ca2+ sensitivity of the SR Mg(2+)-ATPase. Fifty percent activation was shifted from a control free [Ca2+] of 0.42 microM at 0.6 mM free [Mg2+] to 0.63 microM free [Ca2+] at 1.2 mM free [Mg2+], conditions that simulate the reperfused stunned myocardium. These results indicate that after stunning the observed decline in SR Ca2+ transport, determined under similar incubation conditions, may be further jeopardized by the sustained increase in free [Mg2+].(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

Effects of an increase in intracellular free [Mg2+] after myocardial stunning on sarcoplasmic reticulum Ca2+ transport.

BACKGROUND: Myocardial stunning has been associated with a greater than twofold increase in intracellular free [Mg2+] from 0.6 to 1.5 mM. The effect of this increase in free [Mg2+] on the function of the sarcoplasmic reticulum (SR) Ca2+ pump was assessed in SR isolated from Langendorff perfused, isovolumic rabbit hearts after 15 minutes of global ischemia. METHODS AND RESULTS: Our results indicate that myocardial stunning results in a shift in the Ca2+ sensitivity of oxalate-supported, Ca2+ transport over the entire range of free [Ca2+] associated with the cardiac cycle. Using 0.6 mM free Mg2+ as control, maximal rates of Ca2+ transport occurred at 1 microM free Ca2+ (control, 519 +/- 32; stunned, 337 +/- 37 nmol Ca2+.min-1.mg-1). At 0.56 microM free Ca2+, SR Ca2+ transport was reduced from a control of 351 +/- 49 to 263 +/- 12 nmol Ca2+.min-1.mg-1 at 0.6 mM free [Mg2+]. Moreover, an increase in the free [Mg2+] from 0.6 to 1.5 mM results in a greater shift in the Ca2+ activation curve with no change in the level of maximal activation. Ca2+ transport at 0.56 microM free Ca2+ was shifted in the stunned SR from 263 +/- 12 to 138 +/- 29 nmol Ca2+.min-1.mg-1 at 0.6 and 1.5 mM free Mg2+, respectively. CONCLUSIONS: These results indicate that an increase in free [Mg2+] after stunning in combination with the inherent defect in the SR Ca2+ ATPase may reduce the ability of the cell to regulate Ca2+ to a greater extent than previously observed. This impairment in Ca2+ regulatory function may contribute directly to the increase in diastolic tone and indirectly to the reduced systolic function characteristic of the stunned myocardium.

Animals↗
PubMed1990

Effect of global myocardial stunning on Ca2(+)-sensitive myofibrillar ATPase activity and creatine kinase kinetics.

Reperfusion of rabbit hearts after 15 min of global ischemia at 37 degrees C depressed developed pressure by 36% (myocardial stunning). Changes in myofilament function were investigated as causes of this depression. Kinetic analysis of the effects of stunning on myofibrillar catalyzed ATP hydrolysis showed that stunning lowered Michaelis constant (Km) slightly and left maximal enzyme reaction velocity unaltered in the stunned myofilaments. The myofilament end of the creatine kinase (CK) shuttle was also found to be unaffected in the stunned myofibrils. The Km ADP for myofibrillar CK from control and stunned hearts was 60.45 +/- 3.45 and 68.04 +/- 2.42 microM, respectively, and the CK activity at 100 microM ADP was 0.63 +/- 0.08 and 0.67 +/- 0.04 IU/mg myofibrillar protein from control and stunned hearts, a rate three times greater than the myofibrillar adenosinetriphosphatase (ATPase) rate and a rate sufficient to deliver ATP to the myofilaments. Myofilament Ca2+ sensitivity was assessed by measuring Ca2(+)-dependent myofibrillar Mg2(+)-ATPase activity at free [Ca2+] ranging from 10 nM to 32 microM and [Mg.ATP] of 0.8, 1.6, and 3.2 mM. The sensitivity of myofilaments to activation by Ca2+ was unaltered in the myofibrils isolated from stunned hearts. It is concluded from these analyses that the depression of pressure development observed in stunned hearts is not due to a defect in myofilament function.

Adenosine Triphosphatases↗
PubMed1989

Alterations in cardiac sarcoplasmic reticulum calcium transport in the postischemic "stunned" myocardium.

This study examined the possibility that the postischemic mechanical depression observed in the "stunned" myocardium is a result of an alteration in the control of intracellular calcium. Regional myocardial stunning was produced in five open-chest dogs by eight to twelve 5-minute occlusions of the left anterior descending coronary artery, alternated with 10-minute reflow periods and followed by a final 60-minute period of reperfusion. Systolic segment shortening in the postischemic zone, measured by sonomicrometry, fell from 14.9% at baseline to -1.1% at the end of reperfusion. Sarcoplasmic reticulum isolated from stunned myocardium demonstrated a 17% reduction in oxalate-supported 45Ca2+ transport compared with sarcoplasmic reticulum from normal myocardium (0.93 vs. 1.12 mumol Ca2+/mg protein/min, p less than 0.005). There was also a 20% decrease in the maximal activation by Ca2+ of the sarcoplasmic reticulum Ca2+, Mg2+-ATPase (2.46 vs. 1.96 mumol Pi/mg protein/min, p less than 0.005), and a downward shift in the Ca2+-activation curve of the Ca2+, Mg2+-ATPase. These results indicate that myocardial stunning is associated with damage to the calcium-transport system of the sarcoplasmic reticulum. Altered intracellular control may contribute to the inability of the stunned heart to maintain normal mechanical function.

Animals↗
PubMed1985

The effect of short term normothermic global ischemia and acidosis on cardiac myofibrillar Ca2+-Mg2+ ATPase activity.

There is now good evidence to indicate the onset of myocardial ischemia is accompanied by a decline in intracellular pH which parallels the decrease in tension development. The component of the excitation--contraction coupling system which is responsible for the loss in tension development has not been determined although the contractile proteins are a likely candidate since the calcium sensitivity of tension development and of myofibrillar ATPase are both inhibited by a decrease in pH. However, these studies have utilized normal tissues and the effects of pH compounded with ischemia have not been determined. It is plausible to suggest that there may occur ischemic damage to the excitation--contraction coupling system which would depress function in a manner distinct from that incurred by acidosis. Toya-Oka and Ross have demonstrated a loss in regulatory proteins during regional ischemia, suggesting an effect of ischemia independent of pH. We recently demonstrated, in sarcoplasmic reticulum isolated from ischemic myocardium, a defect in function which could not be accounted for solely on the decrease in pH. It was, therefore, the purpose of this study to determine the effects of decreasing pH on cardiac myofibrillar ATPase activity isolated from hearts which had been subjected to short-term, global normothermic ischemia. This design permits us to answer the following questions: Is there a decrease in myofibrillar ATPase activity in the canine heart following 30 min of normothermic global ischemia? Does acidosis play a contributory role in any observed depression of myofibrillar ATPase activity during ischemia? and Does the ischemic process, independent of acidosis, produce a further depression of myofibrillar ATPase activity?

Acidosis↗
PubMed1981

Excitation-contraction coupling in hypothermic ischemic myocardium.

The excitation-contraction coupling system of the global ischemic hypothermic myocardium was studied by evaluating the functional integrity of the isolated sarcoplasmic reticulum (SR) and myofibrils and determining glycogen decay 30 and 60 min after the onset of surgically induced global ischemia. Calcium uptake by the SR from both the 30- and 60-min groups was depressed (control 0.940 +/- 0.05, 30 min 0.430 +/- 0.033, 60 min 0.535 +/- 0.033 mumol Ca2+ . mg-1 . min-1; P less than 0.001). In contrast SR Ca2+-ATPase activity was not different in the three groups (control 1.150 +/- 0.080, 30 min 1.468 +/- 0.025, 60 min 1.338 +/- 0.199 mumol Pi . mg-1 . min-1; P greater than 0.2). Glycogen decay in the hypothermic group was depressed compared to control (control 7.52 +/- 2.01, 30 min 6.152 +/- 1.16, 60 min 5.814 +/- 1.76 mumol glycogen/mg myocardium; P less than 0.05). Myofibrillar pCa-ATPase curves in both hypothermic ischemic groups were depressed (maximal ATPase activity; control 0.160 +/- 0.028, 30 min 0.1130 +/- 0.01, 60 min 0.127 +/- 0.008 mumol Pi . mg-1 . min-1; P less than 0.01). Kinetic analysis of the myofibrillar pCa-ATPase data, utilizing double-reciprocal plots, demonstrated an increase in Km for the hypothermic ischemic groups. It is concluded that the excitation-contraction coupling system of the hypothermic ischemic myocardium at 1 h is characterized by a defect in the calcium transport system of the sarcoplasmic reticulum with preservation of the Ca2+-ATPase, a depression of the myofibrillar ATPase activity, a decrease in affinity, and the preservation of adequate glycogen stores. It is hypothesized that these defects may explain an observed depression in myocardial function following reperfusion.

Adenosine Triphosphatases↗
PubMed1981

Augmented venous return: a model of left ventricular afterload reduction during the course of endotoxin shock.

Utilizing a canine model of endotoxin shock (E coli, 4 mg/kg, B6:026) the major determinants of cardiac output (preload, afterload, contractility, and heart rate) were simultaneously followed for 5 hr in four study groups: Group I: time-matched controls, Group II: endotoxin shock, Group III: endotoxin shock and femoral-femoral A-V shunt, and Group IV: A-V shunt control. Groups II and III demonstrated an initial, abrupt increase in total peripheral resistance (TPR), coronary vascular resistance (CVR), and pulmonary vascular resistance (PVR), and a decrease in cardiac output (CO), coronary flow (CF) and heart rate (HR) and stroke work (P less than 0.05). Group II then demonstrated a decrease in TPR, CVR, PVR with an increase in CO and CF but systemic arterial pressure did not return to control values. At approximately 3 hr, Group II developed a progressive increase in TPR, CVR, and PVR, and a decrease in CO, CF, and SW. Heart rate did not change. In contrast, at 3 hr Group III demonstrated no significant increase in TPR, CVR, or PVR, a progressive increase of CO and CF, and preservation of SW. It is hypothesized that endotoxin shock is characterized by an initial phase characterized by an increase in resistance and decrease in flow that is not affected by an augmented venous return. However, in the intermediate and latter stages of shock, there is a progressive increase in resistance and decrease in flow, increasing impedance to left ventricular ejection that results in an imbalance between myocardial oxygen supply and demand, contributing to the observed myocardial failure. An augmented venous return, by decreasing resistance (afterload) and increasing venous return (preload) preserves cardiac output and myocardial function and thus serves as a model of left ventricular afterload reduction during the course of endotoxin shock.

Animals↗
PubMed1980

Myocardial failure and excitation--contraction uncoupling in canine endotoxin shock: role of histamine and the sarcoplasmic reticulum.

Subendocardial and subepicardial sarcoplasmic reticulum (SR) were isolated from five groups of dogs following five hours of hemodynamic monitoring: Group 1, 6-8 mg/kg diphenhydramine (n = 5); Group 2, 0.5 mg/kg histamine phosphate, IV bolus; Group 3, 4.0 mg/kg Escherichia coli endotoxin (n = 5); Group 4, 6-8 mg/kg diphenhydramine, followed by 4.0 mg/kg E coli endotoxin (n = 5); and Group 5, time-matched, sham-operated controls (n = 5). The velocity of calcium uptake and ATP hydrolysis and the integrity of the transport system were determined (coupling ratio = mumoles Ca++/mumoles Pi). Control SR calcium-uptake velocities averaged 1.13 +/- 0.3 mumoles Ca++/mg-min, with no significant difference between the endocardium and epicardium. SR calcium uptake from the endotoxin shock group averaged 0.64 +/- 0.06 (endocardium) and 0.56 +/- 0.05 (epicardium) mumoles Ca++/mg-min (P < 0.01 from control).ATPase activity from the control group = 1.23 +/- 0.04 mumoles Pi/mg-min; and the endotoxin-shocked group exhibited an activity of 0.99 +/- 0.06, with no significant difference between the endocardial and epicardial populations (P > 0.1). Diphenhydramine-control SR calcium-uptake rates averaged 1.12 +/- 0.6 mumoles Ca++/mg-min, with no difference between endocardium and epicardium. Diphenhydramine pretreatment plus endotoxin-shock epicardial SR calcium uptake = 0.94 +/- 0.08 mumoles Ca++/mg-min, while the endocardial SR was significantly depressed at 0.72 +/- 0.04 mumoles Pi/mg-min, with no difference between endocardium and epicardium. Bolus histamine infusion resulted in a small but significant depression of both SR calcium-uptake rates (0.93 +/- 0.04 mumoles Ca++/mg-min) and ATPase activity (0.93 +/- 0.04 mumoles Pi/mg-min), with no significant difference between epicardium and endocardium. This study confirms that the calcium transport system of cardiac sarcoplasmic reticulum isolated from endotoxin-shocked animals is depressed. However, this depression is not due entirely to a depression of the Mg++-dependent, Ca++-stimulated ATPase enzyme, but is also associated with a significant uncoupling of ATP hydrolysis from calcium transport. The histamine blocker, diphenhydramine, was only able to protect the epicardial SR; the endocardial SR still exhibited an uncoupling of ATP hydrolysis from calcium transport. Bolus histamine infusion produced a small but significant depression of both calcium transport and ATP hydrolysis. These results are formulate d into a "proton-lysosome" hypothesis that appears to be able to explain excitation-contraction uncoupling in the endotoxin-shocked myocardium.

Animals↗