Biomedical subjects

A Meissner

Publications and source records attributed to A Meissner.

At least 55 records · Page 3Linked to original sources

PubMed1999

Pulse sequences for measurement of one-bond (15)N-(1)H coupling constants in the protein backbone.

A set of three improved two-dimensional (2D) NMR methods for measuring one-bond (15)N-(1)H coupling constants in the protein backbone is presented. They are tailored to suit the size of the TROSY effect, i.e., the degree of interference between dipolar and chemical shift anisotropy relaxation mechanisms. The methods edit 2D spectra into two separate subspectra corresponding to the two possible spin states of the coupling partner. Cross talk between the two subspectra is a second order effect in the difference between the actual coupling constants and the one used in setting the pertinent delays of the pulse sequences. This relatively high degree of editing accuracy makes the methods useful for applications to molecules subjected to weak alignment where the one-bond coupling constants are linear combinations of a scalar J and a residual dipolar contribution containing important structural information. A demonstration of the new methods is shown for the (15)N-labeled protein chymotrypsin inhibitor 2 in a lipid bicelle mixture.

Hydrogen↗

PubMed1999

Suppression of diagonal peaks in TROSY-type 1H NMR NOESY spectra of 15N-labeled proteins.

A novel method for suppression of diagonal peaks in the amide region of NOESY NMR spectra of 15N-labeled proteins is presented. The method is particularly useful for larger proteins at high magnetic fields where interference between dipolar and chemical shift anisotropy relaxation mechanisms results in large TROSY effects, i.e. , large differences in 1HN linewidths depending on the spin state of attached 15N nuclei. In this limit the new TROSY NOESY method does not compromise sensitivity. It is demonstrated using a perdeuterated 15N-labeled protein sample, Neural Cell Adhesion Molecule 213-308 (NCAM) from rat, in H2O at 800 MHz.

Animals↗

PubMed1999

Quantification of intracellular metabolic fluxes from fractional enrichment and 13C-13C coupling constraints on the isotopomer distribution in labeled biomass components.

A method for the quantification of intracellular metabolic flux distributions from steady-state mass balance constraints and from the constraints posed by the measured 13C labeling state of biomass components is presented. Two-dimensional NMR spectroscopy is used to analyze the labeling state of cell protein hydrolysate and cell wall components. No separation of the biomass hydrolysate is required to measure the degree of 13C-13C coupling and the fractional 13C enrichment in various carbon atom positions. A mixture of [1-13C]glucose and uniformly labeled [13C6]glucose is applied to make fractional 13C enrichment data and measurements of the degree of 13C-13C coupling informative with respect to the intracellular flux distribution. Simulation models that calculate the complete isotopomer distribution in biomass components on the basis of isotopomer mapping matrices are used for the estimation of intracellular fluxes by least-squares minimization. The statistical quality of the estimated intracellular flux distributions is assessed by Monte Carlo methods. Principal component analysis is performed on the outcome of the Monte Carlo procedure to identify groups of fluxes that contribute major parts to the total variance in the multiple flux estimations. The methods described are applied to a steady-state culture of a glucoamylase-producing recombinant Aspergillus niger strain.

Aspergillus niger↗

PubMed1999

Effects of the calcium channel antagonist mibefradil on haemodynamic parameters and myocardial Ca(2+)-handling in infarct-induced heart failure in rats.

OBJECTIVE: Abnormal intracellular Ca(2+)-handling has been implicated in the pathogenesis of contractile dysfunction and arrhythmias in failing hearts. Calcium channel antagonists (CCA) have been proposed for the prevention of cardiac events after myocardial infarction (MI). Recent studies suggest that the blockade of T-type Ca(2+)-channels induced a heart rate reduction without negative inotropic effects. We investigated the effects of the preferentially T-channel blocking CCA, mibefradil, on haemodynamic parameters and intramyocardial Ca(2+)-handling and contractility in the early and late period after MI. METHODS: MI was induced by permanent ligation of the left coronary artery in male normotensive Wistar rats. Animals were divided in sham-operated and placebo- or mibefradil-treated MI rats. Placebo or Mibefradil treatment (10 mg/kg/d via gastric gavage) was started 7 days prior to MI-induction. Haemodynamic and intramyocardial Ca2+ measurements were performed 1, 3, 7 and 42 days after surgery. At these time points, mean arterial blood pressure (MAP), heart rate (HR), left ventricular enddiastolic pressure (LVEDP) and cardiac contractility (dP/dtmax) were measured in conscious rats. After haemodynamic measurements, the left ventricular papillary muscle was separated to determine developed tension (DT), time to peak tension (TPT) and systolic and diastolic free intracellular Ca2+ concentrations ([Ca2+]i) using the Ca2+ indicator aequorin. Dose-response curves after extracellular isoproterenol- or Ca(2+)-stimulation were recorded. RESULTS: In the early (1-3 days) period after MI, MAP and dP/dtmax were decreased and LVEDP and HR were increased in placebo-treated MI rats. Mibefradil treatment increased MAP and dP/dtmax and decreased LVEDP and HR in infarcted rats. In the papillary muscle of placebo-treated rats, MI induced a decrease in DT and an increase in TPT and in diastolic and systolic [Ca2+]i. DT of placebo-treated MI rats showed a reduced reactivity after isoproterenol- or Ca(2+)-stimulation. After mibefradil treatment DT was increased and TPT was reduced in the late period (7-42 days) after MI, and diastolic and systolic [Ca2+]i were decreased in the early period after MI (1-3 days). The inotropic response to beta-adrenergic or extracellular Ca(2+)-stimulation was markedly improved by mibefradil 7 and 42 days after MI. CONCLUSION: We conclude, that mibefradil improves cardiac function, protects the myocardium against ischemia-induced Ca(2+)-overload and increases beta-adrenergic responsiveness in chronically failing rat hearts.

Adrenergic beta-Agonists↗

PubMed1999

Dantrolene sodium improves the force-frequency relationship and beta-adregenic responsiveness in failing human myocardium.

BACKGROUND: Failing human myocardium is characterized by a negative force-frequency relationship and impaired beta-adrenergic responsiveness which have been related to alterations of the intracellular Ca2+ homeostasis. Dantrolene sodium is a clinically used drug that modulates myocardial [Ca2+]i handling in animal models. This study investigated the effects of dantrolene sodium on intracellular Ca2+ handling and contractile function in failing human myocardium. METHODS AND RESULTS: Twenty-three muscle strips from human left ventricular trabeculae were obtained from patients undergoing heart transplantation for end-stage heart failure caused by idiopathic dilated cardiomyopathy (n = 15). Isometric contraction and intracellular Ca2+ transients (Ca2+ indicator: aequorin) were recorded simultaneously. The experiments were performed in three separate groups exposed to control condition (n = 8), addition of dantrolene (10 micromol/l; n = 8), or addition of verapamil (1 micromol/l; n = 7). Isoproterenol induced a moderate positive inotropic effect in the control group with a maximal increase of developed tension from 10.8 +/- 2.9 to 23.4 +/- 4.7 mN/mm2 and a parallel rise in peak systolic [Ca2+]i to a maximum of 1.36 +/- 0.20 micromol/l. Dantrolene significantly improved (10.2 +/- 3.8 to 32.4 +/- 0.9 mN/mm2) and verapamil blunted (8.3 +/- 2.8 to 17.1 +/- 4.3 mN/mm2) the inotropic response to isoproterenol. The diastolic and systolic [Ca2+]i during isoproterenol stimulation were slightly lower in the dantrolene group but significantly depressed in the verapamil group as compared to the control group. Similarly, analyses of force-frequency relationships revealed an improvement of developed tension in dantrolene-treated as compared to control preparations whereas the peak systolic [Ca2+]i was almost identical. CONCLUSION: Dantrolene improves the negative force-frequency relationship and beta-adrenergic responsiveness in failing human myocardium. These effects are not accompanied by an additional increase in intracellular [Ca2+]i but might be related to modifications of the diastolic [Ca2+]i homeostasis.

Adrenergic beta-Agonists↗

PubMed1999

High thoracic epidural anesthesia, but not clonidine, attenuates the perioperative stress response via sympatholysis and reduces the release of troponin T in patients undergoing coronary artery bypass grafting.

UNLABELLED: In this prospective study, we evaluated whether high thoracic epidural anesthesia (TEA) or i.v. clonidine, in addition to general anesthesia, affects the cardiopulmonary bypass- and surgery-associated stress response and incidence of myocardial ischemia by their sympatholytic properties. Seventy patients scheduled for elective coronary artery bypass graft (CABG) received general anesthesia with sufentanil and propofol. TEA was randomly induced before general anesthesia and continued during the study period in 25 (anesthetized dermatomes C6-T10). Another 24 patients received i.v. clonidine as a bolus of 4 microg/kg before the induction of general anesthesia. Clonidine was then infused at a rate of 1 microg x kg(-1) x h(-1) during surgery and at 0.2-0.5 microg x kg(-1) x h(-1) postoperatively. The remaining 21 patients underwent general anesthesia as performed routinely (control). Hemodynamics, plasma epinephrine and norepinephrine, cortisol, the myocardial-specific contractile protein troponin T, and other cardiac enzymes were measured pre- and postoperatively. During the preoperative night and a follow-up of 48 h after surgery, five-lead electrocardiogram monitoring was used for ischemia detection. Both TEA and clonidine reduced the postoperative heart rate compared with the control group without jeopardizing cardiac output or perfusion pressure. Plasma epinephrine increased perioperatively in all groups but was significantly lower in the TEA group. Neither TEA nor clonidine affected the increase in plasma cortisol. The release of troponin T was attenuated by TEA. New ST elevations > or = 0.2 mV or new ST depression > or = 0.1 mV occurred in > 70% of the control patients but only in 40% of the clonidine group and in 50% of the TEA group. We conclude that TEA (but not i.v. clonidine) combined with general anesthesia for CABG demonstrates a beneficial effect on the perioperative stress response and postoperative myocardial ischemia. IMPLICATIONS: Thoracic epidural anesthesia combined with general anesthesia attenuates the myocardial sympathetic response to cardiopulmonary bypass and cardiac surgery. This is associated with decreased myocardial ischemia as determined by less release of troponin T. These findings may have an impact on the anesthetic management for coronary artery bypass grafting.

Adrenergic alpha-Agonists↗

PubMed1999

Limited upper thoracic epidural block and splanchnic perfusion in dogs.

UNLABELLED: Epidural blockade leads to a sympathetic block in affected segments and an increase of sympathetic out-flow from various unblocked segments. A limited upper thoracic epidural block (LUTEB) is used during coronary artery surgery affecting the cardiac sympathetic fibers cephalad to the fifth thoracic segment. This block does not extend to the sympathetic fibers innervating the gastrointestinal organs. A LUTEB may lead to an increase of sympathetic activity in the unaffected splanchnic sympathetic segments and the decrease in splanchnic blood flow may contribute to gastrointestinal ischemia after cardiac surgery. We tested the hypothesis that a LUTEB decreases splanchnic perfusion in anesthetized dogs. Thirteen dogs were chronically instrumented with aortic and left atrial catheters, which were used for pressure measurement, as well as injection and withdrawal of reference samples. Thoracic epidural catheters were placed under general anesthesia the day before the experiment. Splanchnic blood flow was determined by using colored microspheres. Induction of a LUTEB did not change general hemodynamics in awake dogs. Propofol anesthesia induced an increase in heart rate that was abolished after LUTEB. LUTEB also decreased mean arterial pressure during propofol anesthesia. We conclude that thoracic epidural anesthesia had no effect on splanchnic blood flow. In propofol anesthetized animals, liver blood flow was increased compared with awake animals; however, it did not change after induction of LUTEB. IMPLICATIONS: A sympathetic block in certain segments leads to increased sympathetic output in unblocked segments. For an upper thoracic epidural block, this might lead to impaired splanchnic perfusion. In awake and propofol-anesthetized, chronically instrumented dogs, however, a limited upper thoracic epidural blockade had no compromising effect on gastrointestinal perfusion.

Anesthesia, Epidural↗

PubMed1999

Inotropic effects of diadenosine tetraphosphate in isolated canine cardiac preparations.

We studied the effects of diadenosine tetraphosphate (AP4A) on the force of contraction in canine preparations. The force of contraction was measured in isolated electrically driven (1 Hz) atrial and ventricular cardiac trabeculae from adult dogs. AP4A (100 microM) alone and after prestimulation with 10 nM isoproterenol reduced force of contraction in atrial preparations by approximately 24%. Moreover, AP4A (100 microM) alone and after prestimulation with 10 nM isoproterenol reduced the force of contraction in ventricular preparations by 29 and 29%, respectively. The negative inotropic effects of AP4A were abolished by the A1-adenosine receptor antagonist 1,3-dipropyl-cyclopentyl-xanthine (DPCPX). In summary, in canine myocardium, AP4A alone and after prestimulation with a beta-adrenoceptor agonist exerts negative inotropic effects, which are probably mediated via A1-adenosine receptors.

Animals↗

PubMed1999

Differential effects of mibefradil, verapamil, and amlodipine on myocardial function and intracellular Ca(2+) handling in rats with chronic myocardial infarction.

Mibefradil is a selective T-type Ca(2+) channel blocker that exerts a potent vasodilating but weak inotropic action. The present study compared mibefradil with traditional L-type Ca(2+) channel blockers in regard to the effects of chronic oral administration on hemodynamics, contractility, and intracellular Ca(2+) handling in failing myocardium from postinfarction rats. Male Wistar rats with ligation-induced myocardial infarction were assigned to placebo or treatment with mibefradil (10 mg/kg/day), verapamil (8 mg/kg/day), or amlodipine (4 mg/kg/day) by oral gavage starting 7 days before the induction of myocardial infarction. Six weeks after myocardial infarction, hemodynamic measurements were performed in conscious animals. In addition, isometric force and free [Ca(2+)](i) were determined in isolated left ventricular papillary muscles. Placebo-treated rats exhibited a decreased mean atrial pressure, an increased left ventricular end-diastolic pressure, and a reduced rate of pressure rise compared with sham-operated animals. Mibefradil treatment significantly improved all of these parameters, whereas both amlodipine and verapamil exerted only minor effects. beta-Adrenergic stimulation with isoproterenol (ISO) enhanced contractility and Ca(2+) availability in papillary muscles from sham-operated rats, whereas the ISO-induced inotropic effect in muscles from placebo-treated rats was severely blunted. Chronic mibefradil treatment significantly improved the inotropic response to ISO stimulation, although the Ca(2+)(i) availability appeared to be less than in muscles from placebo-treated animals. In contrast, both verapamil and amlodipine did not restore the inotropic and Ca(2+)(i) modulating effect of ISO in remodeled myocardium. Thus, T-type Ca(2+) current appears to be of pathophysiological relevance in postischemic reperfused myocardium.

Adrenergic beta-Agonists↗

PubMed1999

Duplex screening as a method of quality assurance of perioperative thromboembolism prophylaxis.

BACKGROUND: Improvements in thrombosis prophylaxis in both the operative and non-operative fields aim to reduce further the not inconsiderable residual risk of suffering a deep vein thrombosis or embolism. The goal of the study was to establish the part played in a quality assurance strategy by early diagnosis of a thrombosis and by knowledge of the hospital's internal patient-risk profile in order to counter the unpredictability of thromboembolic complications and make rational decisions about thromboembolism prophylaxis. METHODS: Duplex ultrasonography has been used routinely in trauma surgical patients in Krefeld Hospital since September 1991 as a screening method for diagnosing deep leg and pelvic vein thrombosis prior to mobilisation of the patients. 778 patients were investigated up to March 1997. In the period from September 1991 to September 1994, patients received standardised low-dose prophylaxis with unfractionated heparin (UFH). In October 1994, the prophylaxis regimen was modified by changing the anti-embolism stockings from bidirectional elastic stockings to transverse elastic graduated compression stockings (TED) and by adapting the dosage of the heparin prophylaxis to patient risk, with the use of low molecular weight heparin (LMWH) Certoparin (Mono-Embolex NM) since April 1995. All patients with a deep vein thrombosis were treated immediately with APTT-monitored full heparinisation and immobilisation. RESULTS: In the period from September 1991 to March 1997, an asymptomatic deep vein thrombosis of the lower limbs was diagnosed in 68 cases (8.7%) out of 778 trauma surgical patients by means of routine duplex ultrasound. Using a strategy of duplex screening and immediate anticoagulation/immobilisation, no clinically significant pulmonary emboli occurred in this period. At the same time, the antithrombotic efficacy of the prophylaxis could be improved and assessed objectively by means of duplex screening: with optimal compression stockings and consistent use of risk-adapted UFH prophylaxis, it was possible to reduce the residual thrombosis rate, which was 11.5% (95% CI 7.7-15.2%) with standard UFH prophylaxis, to 8.7 % (95% CI 4.5-12.9%) and ultimately, using the combination of optimal anti-embolism stockings and LMWH prophylaxis, to 6.0% (95% CI 3.0-8.9%) which was significant (p<0.05). The cost-effectiveness analysis resulted in a cost-relation per successfully treated patient of about 1:100 for the diagnosis of a deep vein thrombosis using duplex ultrasound and subsequent heparin treatment compared to the diagnosis and intensive care treatment of a massive pulmonary embolism. CONCLUSIONS: Duplex ultrasound screening for asymptomatic deep vein thrombosis thus proves to be a suitable instrument for internal hospital quality control in thrombosis prophylaxis. Its routine use can be recommended at least in high-risk patients, not only from the medicolegal aspect but also from the purely economic aspect.

Adolescent↗

PubMed1998

Effects of angiotensin II on inotropy and intracellular Ca2+ handling in normal and hypertrophied rat myocardium.

The direct inotropic effect of angiotensin II on the myocardium is still controversial and little information exists as to its potential modification by heart disorders. Therefore, this study performed simultaneous measurements of isometric force and intracellular Ca2+ concentrations ([Ca2+]i) in left ventricular papillary muscles from sham-operated and aortic-banded rats at 10 weeks post-surgery. Angiotensin II (10(-6) M) induced a reduction of peak systolic [Ca2+]i (0.56 +/- 0.03 to 0.48 +/- 0.04 microM; P<0.05) and a parallel but insignificant diminution of developed tension (10.5 +/- 1.3 to 9.6 +/- 0.8 mN/mm2) in normal papillary muscles from sham-operated animals. Hypertrophied papillary muscles from aortic-banded rats demonstrated a significant decline in both peak systolic [Ca2+]i (0.51 +/- 0.02 to 0.44 +/- 0.01 microM; P<0.05) and developed tension (8.4 +/- 1.1 to 6.8 +/- 1.7 mN/mm2; P<0.05) after addition of angiotensin II. The time courses of the mechanical contraction and the intracellular Ca2+ signal were prolonged by angiotension II in both groups. Isoproterenol dose-dependently increased developed tension and peak systolic [Ca2+]i in papillary muscles from sham-operated rats. In contrast, the positive inotropic response to isoproterenol was markedly reduced in hypertrophied muscles despite a seemingly unimpaired increase in peak systolic [Ca2+]i. Pretreatment with angiotensin II (10(-6) M) resulted in a significant attenuation of the systolic [Ca2+]i response to isoproterenol stimulation in both normal and hypertrophied papillary muscles. Neither the bradykinin B2 antagonist icatibent (10(-6) M) nor the nitric oxide (NO) inhibitor L-NMMA (10(-6) M) abolished the depressant effects of angiotension II. Thus, ANG II induces a parallel decline of the mechanical performance and Ca2+ availability in rat myocardium. These effects are more distinct in hypertrophied than in normal muscle and become accentuated during beta-adrenergic stimulation. The underlying mechanism is not associated with the NO pathway but might involve a negative functional coupling between the angiotensin and beta-adrenergic-receptor complex.

Angiotensin II↗

PubMed1998

New multidimensional editing experiments for measurement of amide deuterium isotope effects on Cbeta chemical shifts in 13C, 15N-labeled proteins.

Novel multidimensional NMR pulse sequences for measurement of the three- and four-bond amide deuterium isotope effect on the chemical shifts of 13Cbeta in proteins are presented. The sequences result in editing into two subspectra of a heteronuclear triple resonance spectrum ¿omega(N), omega(Cbeta), omega(Halpha)¿ according to there being a deuterium or a proton attached to 15N for the pertinent correlations. The new experiments are demonstrated by an application to the first module of the 13C,15N-labeled protein RAP 18-112 (N-terminal module of alpha2-macroglobulin receptor associated protein).

Amides↗

PubMed1998

[Comparison of internal fixation methods for the symphysis in multi-directional dynamic gait simulation].

For the stabilization of the ruptured pubic symphysis, rigid forms of fixation such as plate osteosynthesis and flexible fixations such as wire loops or PDS banding have been recommended. All methods have only been tested by static unidirectional loading until failure of the system. By this experimental arrangement Ecke and Hofmann found comparable results for flexible and rigid methods of internal stabilization of the pubic symphysis. They preferred flexible methods to maintain mobility of the symphysis and to prevent symphyseal fusion. We tested dynamic compression plate osteosynthesis, reconstruction plate osteosynthesis, wire loops and PDS banding for internal fixation of injured pubic symphysis in a dynamic multidirectional experimental arrangement simulating gait conditions. The specimens were loaded with 85 N in vertical (y-) direction and 34 N in sagittal (z-) direction, which represent 50% of the forces acting at the pubic symphysis during walking and with a frequency of 1.5 Hz over 55,500 loads simulating the conditions over a 6-week mobilization period. Loading with 100% of the acting forces (corresponding to full weight bearing mobilization) led to early failure of the system. Our experimental analysis showed that neither wire loops nor PDS banding is able to stabilize the ruptured pubic symphysis, even immediately after fixation before loading. During the tests instability increased until failure of the system due to cutting of the bone or breaking of the wires or PDS banding. Success of plate osteosynthesis was dependent on the initial stability of the fixation. Overwinding of the screws, as in osteoporotic bone, lead to increasing loosening during repeated loading, whereas primary stable fixation of the screws was almost completely maintained during the test. In consequence, neither wire loops nor PDS banding should be used for stabilization of injured pubic symphysis if early mobilization with partial weight bearing is desired. Plate osteosynthesis (DC or reconstruction plate) tolerates early half weight bearing in patients with "open-book" injury only if safe screw fixation is guaranteed.

Biomechanical Phenomena↗

PubMed1998

Thoracic epidural anesthesia does not affect functional recovery from myocardial stunning in sevoflurane-anesthetized dogs.

OBJECTIVE: A beneficial effect of thoracic epidural anesthesia (TEA) on recovery from myocardial stunning was previously shown in awake dogs. The aim of this study was to investigate the effects of TEA on recovery from myocardial stunning in sevoflurane-anesthetized dogs. DESIGN: Randomized animal study. SETTING: Animal laboratory of a university hospital. PARTICIPANTS: Chronically instrumented mongrel dogs. INTERVENTIONS: Six dogs were chronically instrumented for measurement of hemodynamics and myocardial wall thickening fraction (WTF). The following experiments were performed on separate days in a crossover fashion: (1) 10 minutes of ischemia of the left anterior descending (LAD) coronary artery during sevoflurane anesthesia without TEA and (2) 10 minutes of ischemia during sevoflurane anesthesia with TEA. MEASUREMENTS AND MAIN RESULTS: WTF was measured awake (baseline) and at predetermined time points until complete recovery of myocardial function occurred. Induction of anesthesia led to a decrease of WTF compared with baseline. Induction of ischemia led to a further decrease of WTF to negative values, which returned to positive values within the first minute of reperfusion. There were no differences between the two experimental conditions at any of the time points measured. In awake dogs, TEA improved the recovery from myocardial stunning compared with the control experiment. There was no difference between conscious dogs with TEA or sevoflurane-anesthetized dogs with or without TEA. CONCLUSION: TEA has no additional protective effect on the recovery of WTF during sevoflurane anesthesia.

Anesthesia, Epidural↗

PubMed1998

[Rehabilitation of psychiatric patients by half-way house admission--a catamnestic study].

In order to observe the course of rehabilitation of mentally ill persons a catamnestic study was done of 16 mainly schizophrenic former residents of the halfway house for mentally ill in Nuremberg. Along with the rehospitalization rate, the criteria for success were progress in the living and working fields. Concerning the course of illness and independent living very good results were found for the rehabilitation course. Reintegration into the working process could be advanced during the stay, stagnated however after the stay. Classifying the course of rehabilitation, overall or partial success was achieved in more than 80% of the patients interviewed. The stay in a halfway house, hence, is a good possibility for medical rehabilitation of younger patients with long-term mental illness. However, it also turned out that out-patient follow-up treatment and care is of great importance for the social relationships of the often isolated patients.

Activities of Daily Living↗

PubMed1998

Heterogeneity of noninvasive arrhythmic risk indicators in patients with ischemic cardiomyopathy.

Noninvasive electrocardiographic variables for arrhythmic risk stratification in chronic heart failure are of great clinical interest but remain highly controversial. This study analyzed repolarization dispersion, heart rate variability, ventricular ectopic activity, and hemodynamic parameters in 30 patients with ischemic heart failure and in 20 normal control subjects. The values for all parameters were distinctly separated between the failure and control group. Left ventricular ejection fraction had a strong relation to ventricular ectopic activity (r = .54), a weak association with repolarization dispersion (r = .29), and seemingly no parallels with heart rate variability (r = .12). However, no linear association could be detected between any of the arrhythmic risk indicators (r = .10-.22), whereas a number of linearly related angiographic-hemodynamic variables readily defined the mechanical risk profile. Thus, alterations of noninvasive arrhythmic risk indicators in heart failure are not uniform, which confounds approaches for a composite ECG risk score in individual patients.

Arrhythmias, Cardiac↗

PubMed1998

Clonidine improves recovery from myocardial stunning in conscious chronically instrumented dogs.

UNLABELLED: Clonidine, an alpha2-adrenergic agonist, has been widely used in anesthesia because of its sedative, analgesic, sympatholytic, and specific hemodynamic effects. The use of clonidine in myocardial ischemia is controversial because of its bradycardic and hypotensive effects. In the present study, we tested the hypothesis that clonidine improves recovery from myocardial stunning in conscious dogs. Seven dogs were chronically instrumented to allow measurement of left atrial pressure (LAP), aortic blood pressure (ABP), left ventricular pressure (LVP), maximal rate of increase of LVP (LVdP/dtmax), and myocardial wall thickening fraction (WTF). The myocardial blood flow was measured using colored microspheres. To compensate for any potential interaction between the two ischemic episodes, experiments were performed on separate days in a cross-over fashion (four animals underwent Condition 1, and three underwent Condition 2 as their first experiment). The ischemic episodes involved 1) 10 min of ischemia of the left anterior descending (LAD) coronary artery without any intervention, and 2) 10 min of LAD ischemia 30 min after 10 microg/kg iv clonidine. WTF was measured before the induction of ischemia or the application of clonidine (baseline) and at predetermined time points until complete recovery of myocardial function. WTF recovered faster during the first 2 h of reperfusion when clonidine was administered. The increase in plasma epinephrine was attenuated by clonidine during ischemia, but there was no change during reperfusion. The increase of plasma norepinephrine levels was attenuated during ischemia and reperfusion. The hemodynamic effects of clonidine did not depress myocardial perfusion or impair myocardial function. IMPLICATIONS: In this study, we investigated the effects of IV clonidine on myocardial stunning in chronically instrumented dogs. Clonidine improved the recovery from myocardial stunning and attenuated increases in catecholamine plasma levels.

Adrenergic alpha-Agonists↗

PubMed1997

Haemodynamic effects of dopexamine and nitric oxide synthase inhibition in healthy and endotoxaemic sheep.

Chronically instrumented awake healthy sheep (n = 6) received the synthetic catecholamine, dopexamine, during or without a background infusion of the nitric oxide synthase inhibitor. L-nitro-arginine-methylester (L-NAME). Three days later, hypotensive-hyperdynamic circulation was induced and maintained by continuous infusion of Salmonella typhosa endotoxin (10 ng/kg per min). After 24 h of continuous endotoxin infusion, the dopexamine L-NAME protocol was repeated. In healthy and endotoxaemic animals with and without nitric oxide synthase inhibition dopexamine caused the same haemodynamic changes: heart rate and cardiac output increased, mean arterial pressure and systemic vascular resistance decreased. L-NAME infusion induced normalisation of the hypotonic-hyperdynamic circulation in endotoxaemic animals. Dopexamine reduced some adverse effects of L-NAME treatment, like increased pulmonary vascular resistance and decreased oxygen delivery. In conclusion the haemodynamic effects of dopexamine are independent of the amount of nitric oxide production. Dopexamine may attenuate some of the adverse effects of nitric oxide synthase inhibition.

Adrenergic beta-Agonists↗