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S Neubauer

Publications and source records attributed to S Neubauer.

At least 145 records · Page 8Linked to original sources
PubMed1991

Effects of endothelin-1 in the isolated heart in ischemia/reperfusion and hypoxia/reoxygenation injury.

The effects of the vasoconstrictor peptide endothelin-1 were examined in the isolated heart during hypoxia, reoxygenation and reperfusion. Isovolumic rat hearts were perfused with Krebs-Henseleit buffer at constant pressure. Cumulative dose-response curves were obtained for endothelin-1 boluses of 0.04 to 400 pmol in five groups of hearts. Coronary flow declined with increasing dosages and was almost abolished at 400 pmol in control hearts. In hearts subjected to mild hypoxia (perfusate PO2 approximately 150 mmHg), the constrictor effect of endothelin-1 was attenuated at moderate dose compared to control hearts (4 vs. 16% flow reduction at 40 pmol; P less than 0.05). The constrictor effect was unaltered in hearts subjected to either 60 min of severe hypoxia (PO2 approximately 35 mmHg) followed by reoxygenation or to 10 min of total ischemia followed by reperfusion (stunning). When hearts were reperfused following 30 min of total ischemia (irreversible injury), the constrictor response to endothelin-1 was potentiated compared to control (e.g. 36 vs. 16% flow reduction at 40 pmol; P less than 0.05). We conclude that endothelin-1 is a potent coronary constrictor in hypoxic, reoxygenated and reperfused heart. The constrictor effect is attenuated during hypoxia, most likely due to the presence of counteracting vasodilator metabolites. During reperfusion, the constrictor effect is unchanged in stunned myocardium, but is augmented in irreversibly injured heart, due to either increased endothelin-1 binding sites or loss of counteracting vasodilator mechanisms such as prostaglandins and/or endothelium-derived relaxing factor.

Animals↗
PubMed1991

[In vivo 31P-cardiac magnetic resonance spectroscopy: methods and the first clinical results].

31P-magnetic resonance (MR) spectra of the heart can be obtained from well-defined myocardial regions by combined MR imaging and variable selected volumes for spectroscopy. 31P-spectra of 33 volunteers and of 43 patients with dilated and hypertrophic cardiomyopathy and with coronary artery disease were quantified using a curve-fitting routine. To optimize our technique, we recorded unsaturated and partially saturated spectra in several volunteers. Relative peak areas and signal-to-noise ratios showed significant changes with varying pulse repetition times. Saturation factors were applied to correct spectra from volunteers and patients for the effects of partial saturation. Under resting conditions, peak areas of volunteers and patients from the various groups were statistically indistinct.

Adult↗
PubMed1991

Effect of mediators on coronary circulation.

A number of vasoactive mediators have been identified in plasma and in the heart. Some of them may be liberated in inflammatory heart disease. The action of mediators on coronary vasculature in various animal models and their potential role in inflammatory heart disease is reviewed. Their role in patients remains to be determined.

Adrenal Glands↗
PubMed1991

The isolated, buffer-perfused ferret heart: a new model for the study of cardiac physiology and metabolism.

The isolated, buffer-perfused ferret heart is a new model for the study of cardiac physiology and metabolism. Compared to the more commonly used isolated heart preparation, the rat heart, the ferret has a lower rate-pressure product due to lower heart rate, a remarkably low coronary flow and almost complete oxygen extraction. The ferret heart remains in stable haemodynamic and metabolic conditions for a longer period of time than the rat heart. ATP contents of the two species are similar, but creatine phosphate content is higher in the ferret while NAD content is much lower.

Adenosine Triphosphate↗
PubMed1991

[Possibilities of ACE inhibitor therapy in acute myocardial ischemia].

Acute myocardial ischemia results from an increased cardiac workload in presence of a critical coronary stenosis (demand ischemia), coronary occlusion (supply ischemia) or a combination of both. It is complicated by cardiac arrhythmias and deterioration of function of ischemic myocardium and results in an increased load and dilatation of non-ischemic myocardium. Cardiac protection in acute myocardial ischemia can be related to preservation of coronary blood flow, function of ischemic and non-ischemic myocardium or prevention of cardiac arrhythmias. In control animals and humans, ACE-inhibitors have no major effect on coronary blood flow. Myocardial ischemia raises plasma-renin-activity, angiotensin I-conversion by passage through coronary circulation, and plasma-angiotensin-II-concentrations. ACE-inhibitors and angiotensin-II-receptor blockers increase coronary blood flow during myocardial ischemia. Other mechanisms (bradykinin potentiation) may be involved. We found a potentiation of the coronary dilatory effect of the neuropeptide neurotensin (which is probably mediated by prostaglandins) by ACE-inhibitor. ACE-inhibitor may delay infarct development in animal experiments and improve function of ischemic myocardium. The importance of early dilatation of non-ischemic myocardium is unknown and it is unclear whether it may be prevented by an ACE-inhibitor as was shown for late dilatation. Studies on the effect of ACE-inhibitors in exercise-induced angina pectoris are controversial. An antiischemic and coronary dilatory effect has been shown by invasive studies in patients. A preliminary study in unstable angina pectoris was positive. Beneficial hemodynamic and antiarrhythmic effects (as well as excessive hypotension, however) have been shown in patients with acute myocardial infarction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

[Experimental and clinical possibilities of MR spectroscopy of the heart].

MR-spectroscopy of the heart is a relatively new technique for the study of various aspects of cardiac metabolism. The majority of results has so far been obtained with the isolated perfused heart. Here, 31P-MR spectroscopy can be employed to measure high-energy phosphate metabolism and intracellular pH repeatedly and non-invasively. Using a technique called saturation transfer, velocities of enzymatic reactions, such as the creatine kinase reaction, can be measured. Intra- and extracellular Na+ and K+ concentrations can be registered with 23Na- and 39K-MR in conjunction with shift reagent. 13C-MR can be used to tackle carbohydrate metabolism. In-situ-R-spectroscopy allows determination of high-energy phosphates in intact large mammals. Clinical applications of MR-spectroscopy remain to be defined; preliminary results indicate high diagnostic and prognostic potential for patients with coronary artery disease and congestive heart failure.

Animals↗
PubMed1990

[Indications for cardio-MRT].

Cardio-MRT provides complex diagnostic information (morphology, function, biochemistry) with little stress for the patient and is therefore used increasingly for clinical diagnosis. There is great need for interdisciplinary studies concerning function, the use of contrast media and spectroscopy.

Animals↗
PubMed1990

Effects of endothelin-1 in isolated perfused rat heart.

We examined the effects of the vasoconstrictor peptide endothelin-1 in the isolated heart and defined interactions of endothelin-1 with other hormone systems. Isolated isovolumic rat hearts were perfused with Krebs-Henseleit buffer at constant pressure. First, the effect of a single bolus of endothelin-1 (4-400 pmol) was followed for 90 min. The effect of high dosages (40 and 400 pmol) of endothelin-1 on coronary flow was biphasic, with an early vasodilator and a late vasoconstrictor component that was irreversible. Second, cumulative dose-response curves were obtained for endothelin-1 boluses of 0.04-400 pmol. Coronary flow declined with increasing dosages and was almost abolished at 400 pmol. Neither alpha- nor beta-blocking agents (phentolamine and propranolol) nor the Ca2(+)-channel blocker nifedipine altered the effects of endothelin-1, but prostaglandin synthesis inhibition by indomethacin significantly augmented vasoconstriction by endothelin-1. Angiotensin-converting enzyme (ACE) inhibition by captopril antagonized endothelin-1-dependent vasoconstriction to a small extent at 400 pmol. Coronary constriction due to endothelin-1 could not be reversed by nitroglycerin. We conclude that in isolated rat heart endothelin-1 causes marked and long-lasting coronary constriction. The effect is not influenced by sympathetic and Ca2(+)-channel blockade, is enhanced by prostaglandin synthesis inhibition, and is reduced by ACE inhibition.

Adrenergic alpha-Antagonists↗
PubMed1990

Effects of endothelin-1 in the isolated heart under ischemic and cardioplegic conditions.

We examined the effects of the vasoconstrictor peptide endothelin-1 in isolated hearts under ischemic and cardioplegic conditions. Isolated isovolumic rat hearts were perfused with Krebs-Henseleit buffer at constant pressure. Cumulative dose-response curves were obtained for endothelin-1 boluses of 0.04-400 pmol in four groups of hearts. Coronary flow decreased with increasing dosages and was almost abolished at 400 pmol in control hearts perfused at a constant pressure of 100 mm Hg. In hearts made ischemic by reducing coronary perfusion pressure to 35 mm Hg, thus reducing coronary flow by 76%, the constrictor effect of endothelin-1 was well preserved. The endothelin-1 dose-response curve was unaltered when hearts were perfused with buffer containing 30 mM KCl to abolish mechanical activity without reducing extracellular Ca2+ concentration. A fourth group of hearts was perfused with Ca2(+)-free buffer, thus eliminating the source of extracellular Ca2+ as well as mechanical activity. In this group, the constrictor response to endothelin-1 was largely, but not completely, abolished, with a maximal constrictor effect of only 19% as opposed to 87% in control hearts. We conclude that in isolated rat heart endothelin-1 is a potent coronary constrictor under ischemic perfusion conditions and that absence of mechanical activity does not affect the action of endothelin-1, for which the presence of extracellular Ca2+ is essential. The small residual constrictor response with Ca2(+)-free perfusion is probably due to release of Ca2+ from intracellular stores.

Animals↗
PubMed1989

Verapamil attenuates ATP depletion during hypoxia: 31P NMR studies of the isolated rat heart.

To test whether verapamil protects myocardial high-energy phosphate content during hypoxia by reducing pre-hypoxic cardiac work or secondary to metabolic events that occur during hypoxia, we compared the relation between myocardial performance and high-energy phosphate content during normoxia, hypoxia and reoxygenation using 31P NMR spectroscopy in isolated, isovolumic buffer-perfused rat hearts. Function was reduced either by supplying verapamil or by altering work mechanically. During normoxia, supplying verapamil (10(-6.5) to 10(-5) M) decreased cardiac performance, increased both creatine phosphate content and intracellular pH, but had no effect on ATP content. During hypoxia, supplying verapamil attenuated ATP and creatine phosphate depletion, and during reoxygenation, ATP content was higher in verapamil-supplied hearts. In hearts in which pre-hypoxic performance was reduced mechanically, high-energy phosphate content during hypoxia and reoxygenation was preserved to the same extent as in hearts treated with 10(-6.5) M verapamil. During reoxygenation, neither verapamil-pretreatment nor mechanical reduction of pre-hypoxic performance affected the creatine phosphate content or indices of cardiac performance, expressed as percentage of pre-hypoxic values. Since reducing pre-hypoxic workload, either by supplying 10(-6.5) M verapamil or mechanically, produced indistinguishable effects on ATP and creatine phosphate contents during hypoxia and reoxygenation, we conclude that the primary mechanism of action of verapamil in hypoxic injury in the buffer-perfused rat heart is the reduction of pre-hypoxic energy demand.

Adenosine Triphosphate↗
PubMed1988

Velocity of the creatine kinase reaction decreases in postischemic myocardium: a 31P-NMR magnetization transfer study of the isolated ferret heart.

Recovery of postischemic function may be limited by energy synthesis by mitochondria, energy transfer via the creatine kinase reaction, or energy utilization at myofibrils. To identify the limiting step, we defined the relations among oxygen consumption, creatine kinase reaction velocity and cardiac performance in myocardium reperfused following mild, moderate, and severe ischemia. Isolated isovolumic ferret hearts were perfused with Krebs-Henseleit buffer at 37 degrees C. After 30 minutes of control, hearts were made ischemic for 20, 40, or 60 minutes and reperfused for 40 minutes. During preischemia, cardiac performance (estimated as the rate-pressure product), was 14.8 x 10(3) mm Hg/min, oxygen consumption was 16.7 mumol/min/g dry weight, and creatine kinase reaction velocity measured by 31P-nuclear magnetic resonance saturation transfer was 12.7 mM/sec. For hearts reperfused after 20, 40, or 60 minutes of ischemia, rate-pressure product was 11.5, 6.5, and 1.1 x 10(3) mm Hg/min; oxygen consumption was 13.5, 14.2, and 6.9 mumol/min/g dry weight; and creatine kinase reaction velocity was 9.6, 5.0, and 2.0 mM/sec, respectively. Thus, with increasing severity of insult, creatine kinase reaction velocity decreased monotonically with performance (r = 0.99). Changes in creatine kinase reaction velocity were predicted from the creatine kinase rate equation (r = 0.99; predicted vs. measured velocity) and can therefore be explained by changes in substrate concentration. Oxygen consumption did not correlate with performance or creatine kinase velocity, consistent with abnormalities in mitochondrial energy production. In all cases, creatine kinase reaction velocity was an order of magnitude faster than the maximal rate of ATP synthesis estimated by oxygen consumption. We conclude that, in postischemic myocardium, creatine kinase reaction velocity decreases in proportion to performance, but high-energy phosphate transfer does not limit availability of high-energy phosphate for contraction.

Animals↗
PubMed1985

Deterioration of metabolic coronary regulation in hemorrhagic shock. Role of hypoxia and the renin-angiotensin system.

The effect of hypoxia and the renin-angiotensin system on metabolic coronary regulation in hemorrhagic shock was studied in 22 anesthetized open-chest dogs. Left circumflex coronary blood flow was measured with an electromagnetic flowmeter. Dogs were ventilated with room air (n = 8) or 100% oxygen (n = 7). A third group of dogs was ventilated with room air and bilaterally nephrectomized 5 h prior to starting the experimental protocol (n = 7). After control data had been obtained, dogs were bled from the femoral arteries into a pressurized reservoir which maintained blood pressure at 45 +/- 1 mmHg. The angiotensin II receptor blocker, saralasin, was then infused i.v. (0.1, 1.0, 10.0 micrograms/kg per min). Coronary blood flow was reduced by hemorrhage, and no significant difference existed in coronary flow during hemorrhage among the three groups. Coronary sinus oxygen saturation was diminished in control animals during hemorrhage from 26% +/- 1% to 17% +/- 1% (P less than 0.05) but normal in 100% oxygen ventilated animals (30% +/- 3%) and in nephrectomized dogs (34% +/- 4%). Coronary oxygen extraction was reduced by saralasin in intact but not in nephrectomized dogs. In six additional experiments, in which blood pressure was not artificially held constant during saralasin infusion, saralasin still significantly improved coronary sinus oxygen saturation and thus reduced coronary oxygen extraction. The data suggest that both hypoxia and the renin-angiotensin system participate in the restriction of metabolic coronary regulation in hemorrhagic shock.

Animals↗
PubMedDate not supplied

Extracellular volume and transsarcolemmal proton movement during ischemia and reperfusion: a 31P NMR spectroscopic study of the isovolumic rat heart.

We have measured, directly and simultaneously, changes in extracellular volume and intra- and extracellular pH during ischemia in the isolated rat heart using 31P NMR spectroscopy. Hearts were perfused with buffer containing 15 mM sodium phenylphosphonate at pH 7.4. Wash in and wash out experiments showed that phenylphosphonate entered only the extracellular (interstitial, vascular and chamber) space of the heart and had no adverse effects on myocardial energetics, contractile function or coronary flow rate. Hearts were subjected to 28 min of total, global ischemia, during which the phenylphosphonate resonance area in the 31P NMR spectra decreased by 83%, indicating that extracellular fluid had moved rapidly from the heart to the bath surrounding the heart, partly as a result of vascular collapse. A separate, morphological study confirmed that 95% of the vasculature had collapsed by 28 min ischemia. Intra- and extracellular pH were determined from the chemical shifts of the P(i) and the phenylphosphonate resonances, respectively. In the pre-ischemic rat heart, intracellular pH was 7.15 +/- 0.03 and extracellular pH was 7.39 +/- 0.03. By 4 min of ischemia, intra- and extracellular pH were the same and decreased concomitantly throughout the remainder of ischemia to final values of 6.09 +/- 0.19 and 6.16 +/- 0.23, respectively. On reperfusion, the extracellular volume and pH returned to pre-ischemic levels within 1 min, but restoration of intracellular pH took > 2.5 min. Thus, a large volume of extracellular fluid moves out of the rat heart to the surrounding bath and the intra- and extracellular pH become the same during total, global ischemia.

Adenosine Triphosphate↗