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Biomedical subjects

S T Wu

Publications and source records attributed to S T Wu.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1988

Substrate regulation of the nucleotide pool during regional ischaemia and reperfusion in an isolated rat heart preparation: a phosphorus-31 magnetic resonance spectroscopy analysis.

Isolated rat heart preparations were studied to characterise the alterations in high energy phosphates that occur during reversible regional ischaemia and to determine whether pyruvate, as the sole exogenous energy substrate, would attenuate the ischaemia induced depletion of the nucleotide pool when compared with glucose. Using phosphorus-31 magnetic resonance spectroscopy baseline concentrations of adenosine triphosphate, phosphocreatine, inorganic phosphate, and intracellular pH were compared with values during 30 min of left coronary artery occlusion followed by 30 min of reperfusion. These variables were related to changes in developed pressure, coronary flow, and oxygen consumption. In addition, the total nucleotide pool was evaluated by biochemical analysis of myocardial tissue extracts and coronary effluent. The ischaemic region was characterised by a dye staining technique and cross sectional echocardiographic measurements of regional myocardial wall thinning. In both glucose and pyruvate perfused groups, coronary flow and oxygen consumption decreased to 50-60% of control within 1 min of ischaemia and returned to baseline values with reflow. Developed pressure decreased to 50(9) and 74(8)% (mean(SEM] of control after 30 min of ischaemia in glucose and pyruvate perfused groups respectively. Reperfusion resulted in complete recovery of developed pressure in hearts perfused with pyruvate but not in the glucose group. Glucose perfused hearts had a greater decrease in intracellular pH during ischaemia (7.07(0.01) to 6.36(0.1] than pyruvate perfused hearts (7.06(0.02) to 6.83(0.04]. Reperfusion resulted in a rapid return to baseline intracellular pH in both groups. During ischaemia, adenosine triphosphate values decreased to a greater degree in glucose than in pyruvate perfused hearts (57(4) and 79(5)% of baseline respectively). Thirty minutes of reperfusion did not significantly improve adenosine triphosphate concentrations in either group. Phosphocreatine concentrations decreased to 52(7) and 75(6)% of baseline in glucose and pyruvate perfused groups respectively after the ischaemic period. Reperfusion resulted in normalisation of phosphocreatine values in the pyruvate but not in the glucose perfused group. Biochemical analysis of myocardial tissue extracts confirmed the spectroscopy data and showed that pyruvate inhibits the efflux of adenine nucleotide derivatives. Tissue concentrations of adenosine monophosphate were three times greater and adenosine 50% less after 30 min of ischaemia in the pyruvate perfused group.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Improvement in myocardial performance without a decrease in high-energy phosphate metabolites after isoproterenol in Syrian cardiomyopathic hamsters.

To determine the effect of isoproterenol on cardiac energetics and function in an animal preparation of cardiomyopathy, we studied Langendorff perfused hearts from Syrian cardiomyopathic hamsters. High-energy phosphate metabolites (phosphocreatine [PCr], ATP, inorganic phosphate [Pi]) and intracellular pH (pHi) were measured by 31P nuclear magnetic resonance spectroscopy and correlated with left ventricular developed pressure, coronary flow, and O2 consumption before and during a 10(-6)M infusion of isoproterenol. Total intracellular calcium was also determined by atomic absorption spectroscopy with the use of potassium ethylenediamine tetra-acetate cobaltate as a marker for extracellular space. In cardiomyopathic hamsters, isoproterenol infusion increased mean developed pressure by 300% (p less than .005 compared with control; n = 5), O2 consumption eightfold (p less than .0005), and PCr by 40% (p less than .05). PCr/Pi ratio, which is analogous to phosphorylation potential, improved 100% (p = .05). In normal hamsters, isoproterenol infusion resulted in an 83% increase in developed pressure (p less than .001) and a 25% increase in O2 consumption (NS). However, mean PCr and PCr/Pi decreased by 30% and 50%, respectively (p less than .05 for both), during isoproterenol infusion. pHi decreased in normal animals (p less than .01), but tended to improve in diseased animals (NS) during isoproterenol infusion. Freeze-clamp measurements of phosphate metabolites correlated well with the nuclear magnetic resonance data. Intracellular calcium increased from 0.0102 +/- 0.002 to 0.144 +/- 0.030 mumol/ml heart water in normal hamsters during isoproterenol infusion. Cardiomyopathic hamsters had a markedly elevated baseline calcium content of 60.82 +/- 5.85 mumol/ml heart water due to the presence of dystrophic calcification.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1987

Factors influencing myocardial response to metabolic acidosis in isolated rat hearts.

We assessed the effects of metabolic acidosis in Langendorff rat hearts to identify factors influencing myocardial response to metabolic acidosis. Intracellular pH (pHi), beta-ATP, phosphocreatine, and inorganic phosphate (Pi) content were measured by 31P nuclear magnetic resonance spectroscopy along with simultaneous measurements of coronary flow and developed pressure during 30 min of perfusion at pH = 6.8, followed by 15 min of reequilibration at pH = 7.4. Under high work-load conditions, pHi, high-energy phosphates, coronary flow, and developed pressure were severely reduced during metabolic acidosis. Each of these hearts exhibited a progressive decline in developed pressure and stopped beating during reequilibration. Lowering work load prevented severe biochemical or mechanical deterioration, allowing complete recovery during reequilibration. In the presence of high work load, factors found to improve myocardial tolerance to metabolic acidosis included maintaining base-line or higher levels of coronary flow with vasodilators or substitution of pyruvate for glucose as the energy-producing substrate. Raising perfusate osmolality did not prevent severe decreases in coronary flow and developed pressure during acidosis, but did allow a dramatic recovery during reequilibration. Recovery of biochemical and mechanical performance after 30 min of metabolic acidosis was directly related to 1) ln[ATP]/[ADP]f[Pi] greater than or equal to 4.1, where [ADP]f is the concentration of free ADP; 2) pHi greater than 6.40; and 3) ATP level greater than or equal to 75% of control.

Acidosis↗
PubMed1985

A polymeric prostaglandin (PGBx) attenuates adenine nucleotide loss during global ischemia and improves myocardial function during reperfusion.

Effects of a synthetic, prostaglandin (PGBx) on energy metabolism in isolated, guinea pig hearts were studied using P-31 nuclear magnetic resonance spectroscopy (NMR) or by direct chemical analysis. Polymeric prostaglandin (500 and 750 ng/ml) attenuated the reduction of ATP and adenine nucleotides during 35 min of total transient ischemia. This occurred despite the absence of any significant preischemic changes in heart rate, contractility or coronary vascular resistance. Preischemic perfusion with PGBx extended the time taken to reach 50% reduction in dP/dt following the first few seconds of ischemia. PGBx had no effect on the development of intracellular acidosis during ischemia. Reperfusion resulted in normalization of phosphocreatine but not ATP concentrations in control and experimental groups. Prostaglandin (750 ng/ml) caused faster and more complete recovery of left ventricular dP/dt following reperfusion. In contrast to untreated hearts, dP/dt in PGBx-treated hearts was significantly higher than preischemic values despite incomplete restoration (70% of control) of ATP levels. These results suggest that the beneficial effects of PGBx observed during myocardial ischemia are unrelated to functionally-induced alterations and that PGBx probably has some direct cellular effect on energy metabolism.

Adenine Nucleotides↗
PubMed1984

Lipid-mediated impairment of normal energy metabolism in the isolated perfused diabetic rat heart studied by phosphorus-31 NMR and chemical extraction.

The relationship between extracellular palmitate and the accumulation of long-chain fatty-acyl coenzyme A with that of high-energy phosphate metabolism was investigated in the isolated perfused diabetic rat heart. Hearts were perfused with a glucose/albumin buffer supplemented with 0, 0.5, 1.2 or 2.0 mM palmitate. 31P-NMR was used to analyze phosphocreatine and ATP metabolism during 1 h of constant-flow recirculation perfusion. At the end of perfusion, frozen samples were taken for chemical analysis of high-energy phosphates and the free and acylated fractions of coenzyme A and carnitine. Perfusion of diabetic hearts with palmitate, unlike control hearts, caused a time-dependent and concentration-dependent reduction in ATP, despite normal and constant phosphocreatine. Concentrations of acid-soluble coenzyme A, long-chain-acyl coenzyme A and total tissue coenzyme A were elevated in palmitate-perfused diabetic hearts, while the total tissue carnitine pool was decreased. Increases in long-chain-acyl coenzyme A correlated with the reduction in myocardial ATP. This reduction in ATP could not be adequately explained by alterations in heart rate, perfusion pressure or vascular resistance.

Acyl Coenzyme A↗
PubMed1984

Salient effects of L-carnitine on adenine-nucleotide loss and coenzyme A acylation in the diabetic heart perfused with excess palmitic acid. A phosphorus-31 NMR and chemical extract study.

The beneficial effects of L-carnitine perfusion on energy metabolism and coenzyme A acylation were studied in isolated hearts from control and diabetic rats. All hearts were perfused at a constant flow rate with a glucose/albumin buffer which contained 2.0 mM palmitate. 31P-NMR was utilized to assess sequential phosphocreatine and ATP metabolism during 1 h of recirculation perfusion. L-Carnitine (5.0 mM final concentration) was added after 12 min of baseline recirculation perfusion. Frozen samples were taken after 1 h of recirculation perfusion for spectrophotometric analysis of high-energy phosphates and the free and acylated fractions of coenzyme A. L-Carnitine perfusion of diabetic hearts attenuated or prevented the reduction of ATP observed in untreated diabetic hearts. It also attenuated the accumulation of long-chain fatty-acyl coenzyme A. Although L-carnitine improved myocardial function in diabetic hearts, this was independent of any direct effect on physiological indices. Thus, the salutory effect of acute perfusion with L-carnitine on energy metabolism in the isolated perfused diabetic rat heart appears to be a direct effect on lipid metabolism.

Acyl Coenzyme A↗
PubMed1983

Abnormal phosphocreatine metabolism in perfused diabetic hearts. A 31P nuclear-magnetic-resonance study.

31P n.m.r. analysis of control and diabetic hearts perfused for 1 h with a glucose buffer showed constant and normal levels of phosphocreatine and ATP. Supplementing the buffer with 0.5, 1.2 or 2.0 mM-palmitic acid had little or no effect on high-energy-phosphate levels in control hearts. In contrast, increases in palmitate concentration produced significant decreases in ATP in diabetic hearts, despite normal and constant levels of phosphocreatine. This 31P n.m.r. study suggests a defect in phosphocreatine metabolism in the perfused diabetic heart that might be related to creatine kinase kinetics.

Adenosine Triphosphate↗
PubMed1983

31P NMR study of erythrocytes from a patient with hereditary pyrimidine-5'-nucleotidase deficiency.

The composition of phosphate metabolites and the intracellular pH in erythrocytes from a patient with hereditary pyrimidine-5'-nucleotidase deficiency were examined using 31P NMR spectroscopy. Several resonances were identified in spectra from intact cells and from extracts. The 2,3-bisphosphoglycerate line intensities were normal but the NTP resonances were about twice normal due to the presence of millimolar quantities of pyrimidine phosphates. Several intense resonances were also observed in the diphosphodiester region of the spectrum. One compound contributing to these lines has been identified as cytidine diphosphocholine. The resonances of NTPs were in a position indicating that the additional triphosphates were also bound by Mg2+. Direct measurement shows that there is a nearly proportional increase in total cell Mg2+ in the patient's cells, in agreement with the interpretation of the spectra. The intracellular pH was about 0.2 unit lower in the patient's erythrocytes. This lower pH is due to the elevation in intracellular fixed negative charges and the shift in permeable anions consequent to the Donnan equilibrium. We suggest that the lower intracellular pH may explain the lower oxygen affinity of these cells in the presence of otherwise normal 2,3-bisphosphoglycerate levels and the increased Mg2+ triphosphates level, because the Mg2+ form of NTPs is known not to alter the oxygen affinity of hemoglobin under physiologic conditions. Furthermore, the lower intracellular pH can also explain the abnormalities in glycolytic intermediates observed for these cells.

5'-Nucleotidase↗
PubMed1981

Measurement of free magnesium in perfused and ischemic arrested heart muscle. A quantitative phosphorus-31 nuclear magnetic resonance and multiequilibria analysis.

The concentration of intracellular free Mg2+ in perfused, beating guinea pig hearts has been estimated on the basis of the Mg2+-dependent separation between the alpha- and beta-phosphorus resonances from 31P NMR spectra of intracellular ATP combined with a computer-assisted analysis of the multiequilibria involved. Measurements and calculations are also used to determine the magnitude of any change in free Mg2+ concentration which may occur during the severe acidosis associated with ischemic arrest. We find the concentration of free Mg2+ to be 2.5 +/- 0.7 mM in control hearts. No significant change was observed during ischemic arrest. These results are discussed in relation to other similar measurements in the literature with detailed consideration given to the value of the MgATP stability constant.

Adenosine Triphosphate↗
PubMed1980

Attenuation of myocardial acidosis by propranolol during ischaemic arrest and reperfusion: evidence with 31P nuclear magnetic resonance.

31P nuclear magnetic resonance (NMR) spectroscopy was used to ascertain whether propranolol could reduce the development of myocardial acidosis during periods of ischaemic arrest and were studied. Cardiac pH progressively declined during ischaemia from a normal 6.97 +/- 0.02 (n = 23) to 6.09 +/- 0.04 or 5.96 +/- 0.04, respectively. Normalisation of pH following reperfusion occurred only in the 35 min ischaemic hearts. Propranolol (1 mg. litre-1) given prior to arrest significantly reduced the magnitude of developing acidosis regardless of the length of ischaemia. Furthermore, it aided in the normalisation of intramyocardial pH upon reperfusion in both groups. Propranolol significantly reduced the magnitude of phosphocreatine (PCr loss normally seen during ischaemic arrest alone, but it did not protect against depletion of ATP. Restoration of PCr reperfusion was virtually complete in all cases, while transient increases in ATP were seen only in those hearts protected by propranolol. In summary, this NMR study demonstrated the first direct evidence that a significant component of the myocardial acidosis caused by global ischaemia and arrest can be blocked by propranolol.

Adenosine Triphosphate↗