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Biomedical subjects

S Kazmaier

Publications and source records attributed to S Kazmaier.

At least 37 records · Page 2Linked to original sources
PubMed1999

Inotropic effects of endothelin-1: interaction with molsidomine and with BQ 610.

-In vivo studies could not detect a positive inotropy of endothelin (ET)-1 as described in in vitro experiments. ET-induced direct positive inotropy, which seems to be mediated by ETB receptors, may be antagonized in vivo by an indirect cardiodepressive effect owing to an ET-induced coronary vasoconstriction via ETA receptors. This study compares the effects of a dose of 1 nmol/kg ET-1 alone on myocardial contractility and myocardial energy metabolism with the effects of 1 nmol/kg ET-1 after pretreatment with 5 mg/kg molsidomine or with 100 microg/kg of the ETA receptor antagonist BQ 610. We investigated the effects of ET-1 versus saline controls in open-chest rats. In addition to measurements in the intact circulation, myocardial function was examined by isovolumic registrations independent of peripheral vascular effects. We also studied the effect of ET-1 on myocardial high-energy phosphates. Pretreatment with molsidomine and BQ 610 attenuated the ET-induced reduction of cardiac output (ET-1: -62%; molsidomine+ET-1: -47%; BQ 610+ET-1: -27% different from controls). After a transient initial vasodilation, ET-1 raised total peripheral resistance (ET-1: +190%; molsidomine+ET-1: +171%; BQ 610+ET-1: +89%). BQ 610 was more effective in preventing ET-induced vasoconstriction. The increase of isovolumic peak first derivative of left ventricular pressure (ET-1: -2%; molsidomine+ET-1: +16%; BQ 610+ET-1: +19%) after pretreatment with molsidomine or BQ 610 indicates that these drugs unmask the positive inotropy of ET-1. ET-induced myocardial ischemia was abolished by molsidomine and BQ 610. Pretreatment with molsidomine or blockade of ETA receptors by BQ 610 can unmask the positive inotropy of ET-1 by preventing ET-induced myocardial ischemia. The positive inotropic effect of ET-1 seems to be mediated by ETB receptors.

Animals↗
PubMed1999

[Does method of anesthesia modify postoperative ischemia incidence? A study of patients after aortocoronary bypass operations].

In the postoperative period after coronary artery bypass graft surgery, the physician's enhanced attention should be focused on the incidence of myocardial ischaemia. The increased stress in the awakening patient as well as the return of autonomous reflexes can be the cause of imbalances in myocardial oxygen supply and uptake. Therefore, a probable influence of the pharmacologic profile of the intraoperatively applied anaesthetics on the incidence of postoperative myocardial ischaemia is of importance for adapting therapy on ICU to minimize any ischaemic risk. After approval by the ethics committee, a prospective randomized study was performed in 40 male patients who underwent coronary artery bypass graft surgery. The aim of the study was to compare balanced anaesthetic techniques performed with fentanyl and halothane, isoflurane and enflurane, respectively, with total intravenous anaesthesia performed with fentanyl and midazolam. An index to classify detection of ischaemia into three categories (ischaemia, probable ischaemia, no ischaemia) was established, based on measurements of myocardial lactate extraction and ST-segment analysis. Simultaneously, measurements of haemodynamic parameters and serum concentrations of catecholamines and intraoperatively applied anaesthetics were taken. In 8% of all measurements (30% of all patients) ischaemia was detected in the observation period and in 37% of all measurements (72.5% of all patients) probable ischaemia was detected. No significant difference was found concerning the incidence of myocardial ischaemia between all groups. The results of this investigation indicate that the application of inhalational anaesthetics for maintaining anaesthesia in coronary artery bypass graft surgery does not increase the risk of postoperative myocardial ischaemia.

Adult↗
PubMed1998

Thrombolytic therapy in acute myocardial infarction: comparison of procoagulant effects of streptokinase and alteplase regimens with focus on the kallikrein system and plasmin.

BACKGROUND: Thrombolytic therapy in patients with acute myocardial infarction (AMI) is hampered by procoagulant effects. In vitro studies have indicated that plasmin stimulation activates the kallikrein-contact-phase system, resulting in thrombin activation. This prospective comparative study was designed to examine the procoagulant effects of streptokinase or alteplase in AMI. METHODS AND RESULTS: Sixty-one patients with AMI received 1.5 million U of streptokinase or front-loaded alteplase (up to 100 mg) and systemic heparin. Twenty-four patients with AMI and no thrombolytic therapy and 30 control subjects were examined for comparison. Molecular markers of thrombin, plasmin activation, and coagulation activities were determined before therapy and serially for up to 10 days. Moderate thrombin (initial thrombin-antithrombin [TAT] complex 18+/-5 versus 4+/-0.3 microg/L, P<0.05) and kallikrein (up to 45+/-4 versus 30+/-1 U/L at 3 hours, P<0.01) activation occurs in patients with AMI. D-Dimers are increased (P<0.01), and plasmin is stimulated (P<0.01). Streptokinase and alteplase increase TAT to 50+/-17 and 51+/-18 microg/L at 3 hours and to 50+/-17 and 33+/-14 microg/L at 6 hours, respectively (P<0.01). Kallikrein activity is elevated (P<0. 01) to 76+/-5 and 71+/-7 U/L at 3 hours and 64+/-6 and 47+/-5 U/L by streptokinase and alteplase, respectively, at 6 hours. Reductions in fibrinogen and increases in D-dimers and plasmin-antiplasmin complexes are more marked (P<0.05 and 0.01) after streptokinase versus alteplase. Correlations were found among TAT, kallikrein activity, and plasmin activation (P<0.01). CONCLUSIONS: The data indicate a more marked procoagulant action of the streptokinase regimen compared with front-loaded alteplase, thus supporting the hypothesis of a plasmin-mediated kallikrein activation with consecutive procoagulant action in vivo.

Acute Disease↗
PubMed1998

Preconditioning preserves energy metabolism in prolonged low-flow ischemia.

BACKGROUND: A reduction in coronary flow leads to a parallel decrease in contractile function. Thus, a flow/function balance is established in the myocardium under certain circumstances avoiding the development of a necrosis (referred to as "hibernating" myocardium). The impact of a preconditioning period on this critical balance was examined. METHODS: In 116 isovolumetrically beating rat hearts, 3 h of hypoperfusion with 15% of control coronary flow were performed followed by 1 h reperfusion; 40 hearts served as controls. As a preconditioning period, in half of the rat hearts a 5 min no-flow ischemia followed by 10 min reperfusion was performed, preceding the prolonged hypoperfusion. RESULTS: Systolic function was identically reduced in both groups after 3 h hypoperfusion (LVP: 39 +/- 2 mmHg, 40 +/- 2 mmHg vs. controls 90 +/- 3 mmHg; p < 0.01). Without preconditioning hypoperfusion resulted in a marked initial decrease in function. This period was followed by an adaptation to a higher steady state level of function compared with non-preconditioned hypoperfused hearts (p < 0.05). After preconditioning hypoperfusion directly resulted in this level of contraction. Contractile reserve was reduced (p < 0.01) identically in both hypoperfusion groups. Adenine nucleotides were decreased (p < 0.01) after 3 h hypoperfusion to 2.1 +/- 0.2 mumol/gww vs. controls (4.7 +/- 0.2 mumol/gww). After initial preconditioning adenine nucleotides were better preserved (3.2 +/- 0.2 mumol/gww) going ahead with a creatine phosphate overshoot of 126% (p < 0.01). After reperfusion, systolic function and contractile reserve were identical in both groups. CONCLUSION: A period of preceding no-flow ischemia followed by reperfusion modifies functional adaptation to hypoperfusion and preserves high energy phosphates. Therefore, the metabolic balance during hypoperfusion is improved by preconditioning, although no impact on contractile reserve or the functional status of reperfused myocardium after low-flow ischemia can be seen.

Adenosine Triphosphate↗
PubMed1998

Inotropic response of stunned hypertrophied myocardium: responsiveness of hypertrophied and normal postischemic isolated rat hearts to calcium and dopamine stimulation.

OBJECTIVE: Severely hypertrophied myocardium was described to have a reduced tolerance towards ischemia. For non-hypertrophied hearts inconclusive findings on the Ca(2+)-responsiveness are reported. Information sensitivity to reversible ischemia and on postischemic Ca(2+)-responsiveness of hearts with clinically common moderate hypertrophy is lacking. Thus, the responsiveness of hypertrophied and normal postischemic myocardium to positive inotropic stimulation should be investigated in the present study. METHODS AND RESULTS: Hearts from spontaneously hypertensive rats (SHR, 4 months old) with significant LV-hypertrophy (+ 50%) and hearts from normotensive 4 months old Wistar rats were investigated using an isovolumic beating isolated heart model (8 hearts/each of the 8 groups). Functional recovery after 30 min of no-flow ischemia was 78 +/- 1% and 77 +/- 3% of preischemic control data in hypertrophied and non-hypertrophied hearts assessed as developed left ventricular pressure (non-ischemic controls: 95 +/- 2% in hypertrophied and 93 +/- 3% in non-hypertrophied controls). Maximum short-term stimulation with Ca2+ revealed a decreased peak left ventricular pressure of 124 +/- 4% in hypertrophied and 120 +/- 5% in non-hypertrophied postischemic hearts, as compared with non-ischemic controls 138 +/- 3% and 157 +/- 5%, respectively ( p < 0.01). A maximum dose of dopamine stimulated hypertrophied and non-hypertrophied postischemic hearts comparable to Ca2+. Analysing the dose-response curve for Ca(2+)-stimulation, the sensitivity expressed as fraction of the maximum was identical in non-ischemic and postischemic myocardium of hypertrophied and non-hypertrophied ventricles in spite of the reduced peak values. CONCLUSION: The findings demonstrate that after moderate reversible ischemia the steady-state function is similarly decreased in hypertrophied and non-hypertrophied postischemic myocardium. The maximum response to Ca2+ is significantly reduced in both types of myocardium, while the Ca2+ sensitivity is unchanged. Identical results after maximum dopamine stimulation as after Ca2+ indicate that the releasibility of Ca2+ and the beta-adrenoceptors are not the critical causes for the postischemic dysfunction in hypertrophied or non-hypertrophied myocardium.

Analysis of Variance↗
PubMed1998

Effects of respiratory alkalosis and acidosis on myocardial blood flow and metabolism in patients with coronary artery disease.

BACKGROUND: Variation of the arterial carbon dioxide partial pressure (PaCO2) is not uncommon in anesthetic practice. However, little is known about the myocardial consequences of respiratory alkalosis and acidosis, particularly in patients with coronary artery disease. The aim of the current study was to investigate the effects of variation in PaCO2 on myocardial blood flow (MBF), metabolism, and systemic hemodynamics in patients before elective coronary artery bypass graft surgery. METHODS: In 10 male anesthetized patients, measurements of MBF, myocardial contractility, metabolism, and systemic hemodynamics were made in a randomized sequence at PaCO2 levels of 30, 40, and 50 mmHg, respectively. The MBF was measured using the Kety-Schmidt technique with argon as a tracer. End-diastolic left ventricular pressure and the maximal increase of left ventricular pressure were assessed using a manometer-tipped catheter. RESULTS: The cardiac index significantly changed with varying PaCO2 levels (hypocapnia, - 9%; hypercapnia, 13%). This reaction was associated with inverse changes in systemic vascular resistance index levels. The MBF significantly increased by 15% during hypercapnia, whereas no change was found during hypocapnia. Myocardial oxygen and glucose uptake and the maximal increase of left ventricular pressure were not affected by varying PaCO2 levels. CONCLUSIONS: In anesthetized patients with coronary artery disease, short-term variations in PaCO2 have significant effects on MBF but do not influence global myocardial oxygen and glucose uptake. Changes in systemic hemodynamics associated with respiratory alkalosis and acidosis are caused by changes in systemic vascular resistance rather than by alterations in myocardial contractility.

Acidosis, Respiratory↗
PubMed1998

Influence of arterial carbon dioxide tension on systemic vascular resistance in patients undergoing cardiopulmonary bypass.

BACKGROUND: The effects of induced hypothermia in cardiac surgical patients are not yet fully understood. Despite numerous studies on the effects of acid-base management on organ blood flow, only little information is available on the effects of alpha-stat versus pH-stat management on systemic haemodynamics. We therefore compared the effect of alpha-stat and pH-stat acid-base management on systemic haemodynamics in a prospective, controlled, cross-over study. METHODS: Twenty patients undergoing coronary artery bypass surgery were included in the study. Cardiac output was measured by thermodilution. Cardiac index and systemic vascular resistance were calculated according to standard formulae. Measurements were performed under hypo- and hypercapnia after induction of anaesthesia. Measurements were repeated at the end of two 30-min periods of pH-stat and alpha-stat acid-base management, respectively. RESULTS: Systemic vascular resistance at the lower PaCO2-levels (hypocapnia and alpha-stat, respectively) was significantly higher than those at the higher level (hypercania and pH-stat, respectively). The periods of different PaCO2-levels were comparable with respect to haematocrit, blood viscosity and temperature. Systemic vascular resistance was not significantly different from the control period. CONCLUSIONS: This study demonstrates that during hypothermic cardiopulmonary bypass, systemic vascular resistance under alpha-stat acid-base management is higher than under pH-stat management. As obvious from measurements during the control period, this finding can be completely explained by the difference in PaCO2.

Aged↗
PubMed1997

[S-(+)-Ketamine and circulation].

The S-(+) isomer of ketamine has about twice the analgesic potency of the clinically used racemic mixture. Therefore, the known side effects may be reduced when one-half of the usual dose is administered. Several prospective, randomised, and double-blinded studies have been performed to assess whether the S-(+) isomer of ketamine is superior to the racemic mixture with respect to circulatory side effects. Studies in young, healthy volunteers showed that heart rate (HR) and arterial blood pressure (ABP) rise significantly after injection of 2 mg/kg ketamine racemate and 1 mg/kg S-(+) isomer without any significant difference between groups. In the study of Doenicke et al. plasma levels of adrenaline (A) were higher in the racemate group, whereas no difference was found in elevated plasma levels of noradrenaline (NA). Premedication with midazolam blunted major haemodynamic changes. The investigation of Adams et al. confirmed that HR and ABP rise significantly after injection of 2 mg/kg ketamine racemate and 1 mg/kg S-(+) isomer without any significant difference between groups. In this study, no differences were found between groups concerning elevated plasma levels of A and NA. A further study in healthy volunteers also showed comparable haemodynamic changes following i.m.injection of 1.0 mg/kg ketamine racemate or 0.5 mg/kg S-(+) isomer without any significant difference between groups. In a previous clinical study including 40 elderly patients undergoing elective orthopaedic surgery, total intravenous anaesthesia (TIVA) was performed with S-(+)-ketamine or ketamine racemate as an analgesic compound. For induction of TIVA, patients received 0.1 mg/kg midazolam and 1 mg/kg S-(+)-ketamine or 2 mg/kg racemic ketamine, respectively. Throughout surgery, a continuous infusion of 2 mg/kg per hour S-(+)-ketamine or 4 mg/kg racemic ketamine was administered. Three patients in the racemate group showed severe arterial hypertension after induction of anaesthesia and were withdrawn from the study. In both groups plasma A and NA levels as well as HR and ABP increased significantly. In our own randomised, double-blinded study, haemodynamic effects of 2 mg/kg S-(+)-ketamine and 4 mg/kg ketamine racemate, respectively, were investigated in 14 patients undergoing elective aorto-coronary bypass surgery. In both groups HR and ABP significantly increased in 3 patients, each although all patients were deeply sedated with midazolam. One patient in the S-(+)-ketamine group showed severe arterial hypertension and tachycardia after induction of anaesthesia and was withdrawn from the study. With respect to haemodynamic changes, the pharmacodynamic effects of ketamine racemate and S-(+)-ketamine are comparable. Therefore, it can be concluded that neither ketamine nor S-(+)-ketamine should be used in patients who suffer, e.g., from arterial hypertension and coronary artery disease.

Anesthetics, General↗
PubMed1997

Effects of positive inotropic stimulation on postischemic myocardium with graded dysfunction.

OBJECTIVE: To investigate the effects of moderate prolonged and of maximum short-term positive inotropic stimulation of postischemic myocardium as a function of the severity of stunning. METHODS: Stunned isolated rat hearts (n = 116) after 30 min and 45 min of ischemia were stimulated with dopamine to raise systolic function (double product) back to control levels. In the isovolumetrically beating hearts, left ventricular developed pressure, double product, dp/dtmax, coronary flow, and myocardial oxygen consumption were determined during steady-state conditions. After maximum stimulation the contractile reserve was examined. Measurements of adenine nucleotides (n = 47) and electron microscopy (n = 9) were made. RESULTS: 30 min ischemia resulted in moderate postischemic dysfunction (LVP 81 +/- 3%; P < 0.05). After 45 min ischemia, function was more severely reduced (LVP 66 +/- 5%; P < 0.01). Coronary flow tended to be lower after ischemia. Myocardial oxygen consumption was not reduced in parallel with the dysfunction. Adenine nucleotides were gradually reduced after ischemia (ATP: 2.5 +/- 0.2 and 1.2 +/- 0.1 vs. 4.2 +/- 0.2 mumol/gww; P < 0.01). Contractile reserve also decreased in relation to the previous ischemic injury (after 45 min ischemia max. LVP 105 +/- 10% vs. max. LVP 152 +/- 8% in controls, P < 0.01). Prolonged stimulation did not result in further reduction in adenine nucleotides and function. CONCLUSIONS: Contractile reserve is decreased in postischemic myocardium in parallel with the previous ischemic burden. Depending on the degree of contractile dysfunction a disturbed function-flow-oxygen consumption relation is present. Prolonged stimulation of stunned myocardium with dopamine back to the control level of function has no harmful short-term effects, indicating sufficient mitochondrial energy generation.

Adenosine Triphosphate↗
PubMed1997

The influence of controlled mandatory ventilation (CMV), intermittent mandatory ventilation (IMV) and biphasic intermittent positive airway pressure (BIPAP) on duration of intubation and consumption of analgesics and sedatives. A prospective analysis in 596 patients following adult cardiac surgery.

The aim of the study was the determination of the influence of ventilation modes on the consumption of analgesics and sedatives, duration of intubation and pulmonary gas exchange. Assist/controlled mandatory ventilation (S-CMV, 123 patients), synchronized intermittent mandatory ventilation (S-IMV, 431 patients) and biphasic positive airway pressure ventilation (BIPAP, 42 patients) were compared in a prospective, controlled, open clinical trial over an 18-month period. Five hundred and ninety-six adult patients with normal pulmonary function before surgery and uneventful course following coronary artery bypass graft surgery were studied. Patients ventilated with BIPAP had a significantly shorter mean duration of intubation (10.1 h, P < 0.05) than patients treated with S-IMV (14.7 h) and S-CMV (13.2 h). In the S-CMV group, 39.9% of the patients required single or multiple doses of midazolam, but only 13.5% in the S-IMV group and 9.5% in the BIPAP group. The mean total amount of midazolam administered to these patients was significantly higher in the S-CMV group (8.8 mg) than in the S-IMV group (6.6 mg, P < 0.05) and in the BIPAP group (4.3 mg, P < 0.05). The consumption of pethidine and piritramide did not differ between S-CMV and S-IMV, but was significantly lower during BIPAP (P < 0.05). After extubation the patients' PaCO2 was highest in the S-CMV group. We conclude that ventilatory support with BIPAP reduces the consumption of analgesics and sedatives, and the duration of intubation. The possibility of unrestricted spontaneous breathing in all phases of the respiratory cycle is considered to be the reason. BIPAP seems to be an alternative to S-CMV and S-IMV in short-term ventilated patient.

Analgesics↗
PubMed1997

[Exitus letalis caused by liquid nitrogen].

A 24-year old student died from asphyxiation while filling flasks with liquid nitrogen. The upper and lower extremities and the back were frozen. The face, ears and neck were livid with a horizontal line of demarcation. A few wide ventricular complexes were seen in the initial ECG, followed by asystole. The patient's trachea was intubated, his lungs ventilated with 100% oxygen and CPR initiated. The site of larynx and pharynx were without pathological findings. 250 ml of a crystalloid solution were infused into the external jugular vein. It was not possible to measure the body temperature. Venous blood gas analysis showed a metabolic acidosis and hyperkaliaemia. CPR was terminated after 90 minutes. Own protection is most important for the rescue team if a nitrogen atmosphere is expected.

Adult↗
PubMed1997

Use of modified fluid gelatin and hydroxyethyl starch for colloidal volume replacement in major orthopaedic surgery.

We have compared 6% hydroxyethyl starch (HES 200/0.5) with 3% modified fluid gelatin (MFG) for volume replacement in major orthopaedic surgery and studied the effects on haemodynamic state, colloid osmotic pressure, blood clotting and plasma homeostasis. Using a controlled, randomized, single-blind clinical design, we studied 46 consecutive patients undergoing major elective orthopaedic hip surgery. The two groups were comparable in age, body weight and duration of surgery. Patients were maintained haemodynamically stable using both HES and MFG over the entire study. Fluid balance and colloidal replacement volumes were comparable in both groups (median perioperative infusion volume: HES 2500 ml, MFG 2400 ml). Laboratory variables were not clinically different. We conclude that both colloidal solutions were comparable in volume efficacy and effects on plasma oncotic pressure, clotting and plasma homeostasis. In the small number of patients studied, 6% HES 200/0.5 was found to be safe when administered in amounts corresponding to the currently accepted maximum daily dose in Germany and France of 33 ml/kg body weight and 2.0 g/kg body weight, respectively.

Adult↗
PubMed1996

[The effect of nitroglycerin on cerebrovascular circulation, cerebrovascular CO2-reactivity and blood flow rate in basal cerebral arteries].

UNLABELLED: The cerebral haemodynamic effects of vasodilators are of clinical interest because a decrease in mean arterial pressure (MAP) might alter global cerebral blood flow (CBF). Luxury perfusion of the brain, contrast, might be unfavourable in patients with reduced intracranial compliance. Despite the widespread use of nitroglycerine (NTG), little is known about the cerebral haemodynamic consequence of NTG infusions in humans. This prospective, controlled study was designed: (1) to investigate the effects of NTG on CBF and cerebrovascular CO2 reactivity and (2) to compare reference measurements of global CBF with transcranial Doppler monitoring (TCD) of middle cerebral artery flow velocity (VMCA). METHODS: With ethical committee approval and informed patient consent, we investigated ten patients undergoing coronary artery bypass surgery. Measurements were performed under fentanyl/midazolam anaesthesia prior to the start of the operation. First, during a baseline period, ventilation was changed in a random sequence to achieve two different levels of arterial PCO2 (30 and 50 mmHg, respectively). Consequently, measurements were repeated during i.v. infusion of 1.5.micrograms.kg-1.min-1 NTG at identifical PCO2 levels. Measurements of CBF were performed by the Kety-Schmidt technique with argon as an indicator. Simultaneously, VMCA was recorded by use of a 2-Mhz transcranial Doppler system. Cerebral perfusion pressure (CPP) was calculated from the difference between MAP and jugular bulb pressure. Statistical analysis was performed by two-way analysis of variance using a repeated-measures design to assess the effects of NTG application and respiratory changes, respectively. RESULTS: During NTG infusion, CPP decreased slightly by 15-17%. Because of a reduction in cerebrovascular resistance, CBF increased at both levels of PaCO2 by 96 and 69%, respectively. However, VMCA decreased concomitantly. Cerebrovascular CO2 reactivity did not change. CONCLUSIONS: This study demonstrates that during fentanyl/midazolam anaesthesia NTG may cause a major increase in CBF as long as CPP does not decrease considerably. Our results further suggest that NTG causes vasodilation of basal cerebral arteries, inducing a discrepancy between relative changes in CBF and VMCA. Consequently, TCD measurements during infusion of NTG should not be directly compared with preceding measurements of MCA flow velocity.

Blood Pressure↗
PubMed1996

[Prevention of postoperative nausea and vomiting with single and repeat administration of ondansetron--review of the literature on different administration forms].

Postoperative nausea and vomiting (PONV) is still a common perioperative complication and ondansetron has proved to be an effective antiemetic substance in its prevention. The antiemetic effect of single and repetitive application was evaluated in this study. Fifty-one female patients who underwent gynaecological surgical procedures took part in a random double-blind study. Before the start of anaesthesia, 21 patients (group 1) received either a placebo (six patients), 8 mg ondansetron orally (seven patients) or 16 mg orally (eight patients). The remaining 30 patients (group 2), split into subgroups of ten, were given the same preoperative medication as group 1 plus further doses of the same strength 8 and 16 hours after the first intake of the study medication. Metoclopramide was given intravenously if patients had more than one emetic episode or if they asked for it. Nausea and vomiting were documented up to 24 hours after finishing anaesthesia. Metoclopramide had only to be given to patients who had received a placebo. Nausea was felt by 57% (4/7) of the patients after a single dose of 8 mg ondansetron and by 40% (4/10) of the patients after three doses of 8 mg. One patient (14%, 1/7) with a single dose and two patients (20%, 2/10) with a repetitive dose of 8 mg ondansetron vomited. Following a single dose of 16 mg ondansetron, no patient (0/8) had to vomit and 25% (2/8) of the patients had nausea. There were no complications reported by the patients. Ondansetron was shown to be a well-tolerated antiemetic and seems to have a higher reductive effect on PONV when given in a single dose and not repetitively. The prophylaxis of vomiting seems to be more effective than the reduction of nausea. Follow-up studies will have to clarify our findings.

Adult↗
PubMed1996

[Clinical use of antiemetic drugs for prevention and therapy of postoperative nausea and vomiting].

The incidence of postoperative nausea and vomiting (PONV) has not decreased significantly for decades. This study was done to evaluate whether there is a standard method or a preferred substance in German hospitals in the prophylaxis and treatment of PONV. Twenty-one randomly selected hospitals were asked to give details about substances, doses and application times and forms in PONV prophylaxis and treatment. Most of the patients with a high risk of emesis were treated prophylactically with droperidol. Dosage and time of application were different in each hospital. Metoclopramide was the second most frequently used substance for both prophylaxis and treatment. Dimenhydrinate, triflupromaxzine, promethazine and acupuncture were used less commonly in prophylaxis. Alizapride and ondansetron were used to treat PONV in only two hospitals. Summarising, this study found no routine standard in the prophylaxis and therapy of PONV. Droperidol and metoclopramide were the most frequently used antiemetics. An overview of the antiemetics involved is given.

Antiemetics↗
PubMed1995

[Hemodynamic effects of new phosphodiesterase inhibitors in patients with coronary heart disease. A comparison between enoximone and R80122].

At present, phosphodiesterase III inhibitors are commonly used for the treatment of low cardiac output states. Despite their positive inotropic and lusitropic effects, these drugs are still under discussion because of certain adverse effects like thrombopaenia, elevation of transaminases, abdominal disregulation, and excessive peripheral vasodilatation. As a consequence, more cardioselective phosphodiesterase inhibitors were developed with the aim of reducing these adverse effects. One of them, enoximone (Marion Merrell Dow, Fig. 1), an imidazole derivative, has nearly no influence on platelets and abdominal organ function. In addition, in many studies vasodilatation was found to be absent. Recently a new substance, R80122 (Janssen, Belgium, Fig. 1), was developed. First experimental studies showed high cardioselectivity of this substance. The aim of this study was to compare the haemodynamic effects of enoximone and R80122 in patients with ischaemic heart disease. METHODS. This study was thoroughly discussed and approved by the local Ethics Committee; all patients gave written informed consent. Twenty male patients (Table 1) with normal left ventricular function who were about to undergo elective coronary artery bypass surgery were randomly allocated to receive a bolus of either 1.0 mg/kg enoximone or 0.3 mg/kg R80122 after induction of anaesthesia. Premedication consisted of 2 mg flunitrazepam orally the evening before and in the morning 1 h before operation. Anaesthesia was induced with 0.007 mg/kg fentanyl, 0.2 mg/kg etomidate, and 0.1 mg/kg pancuronium bromide and maintained by a continuous infusion of 0.02 mg/min fentanyl and 0.3 mg/min midazolam. After induction of anaesthesia haemodynamic measurements were performed and blood gas samples were taken preoperatively under steady-state conditions before and 5, 30, and 60 min after drug administration. RESULTS. The results of both groups are shown in Table 2 as mean values with standard deviations. Individual changes of cardiac index (CI), mean arterial pressure (MAP), and systemic vascular resistance (SVR) are depicted in Fig. 2. Peak percentage changes of the haemodynamic parameters are shown in Fig. 3. Both substances improved cardiac function; 5 min after drug administration CI increased by 31% and 26%, respectively. This was accompanied by increases in stroke volume (13% and 14%, respectively) and heart rate (15% and 10%, respectively). At the same time, there were declines in SVR (38% and 36%, respectively) and MAP (19% and 21%, respectively). Although mean values of pulmonary arterial and wedge pressure decreased after drug administration, these changes were inconsistent and not of clinical relevance. There were no statistically significant differences between the haemodynamic effects of both substances at any time in this study. CONCLUSIONS. Both enoximone and R80122 showed the expected inotropic effects. Nevertheless, both substances have a distinct vasodilative effect, which leads to a decline in MAP. R80122 does not have higher cardioselectivity than enoximone.

Adult↗
PubMed1995

Effect of endothelin-1 and its combination with adenosine on myocardial contractility and myocardial energy metabolism in vivo.

Contradictory results have been reported about the inotropic effects of the vasoconstrictive peptide endothelin-1 (ET-1). In contrast to in vitro experiments, in vivo studies could not demonstrate a positive inotropy of ET-1. It may be possible, that the direct positive inotropic effect of ET-1 observed in in vitro studies is counterbalanced in vivo by an indirect negative inotropy due to its coronar-constrictive effect. This study examined the hemodynamic and inotropic effects of 2500 ng ET-1/kg without and after pretreatment with the vasodilating nucleoside adenosine (0.5, 2.0, 5.0 mg ADO/kg/min). Data were compared with NaCl controls in open-chest rats during and after a 7-min infusion. Besides measurements in the intact circulation isovolumic measurements were carried out for quantification of myocardial contractility independently of peripheral vascular effects. We further examined the effect of ET-1 and its combination with 2.0 mg ADO/kg/min on myocardial high-energy phosphates (ATP, AMP, ADP, creatine phosphate). ET-1 causes a strong and longlasting vasoconstriction (+ 186% v preinfusion values), which is dose-dependently antagonized in part by ADO (+ 109%, + 136%, + 60%). While the maximum of the isovolumic LVSP (peak LVSP) and the corresponding dP/dtmax (peak dP/dtmax) were unchanged with sole ET-1 (peak LVSP: +5%, peak dP/dtmax: -2%), these indexes of myocardial contractility were increased after pretreatment with ADO (peak LVSP: +11%, +13%, +4%; peak dP/dtmax: +9%, +20%, +10%) indicating a positive inotropic effect of ET-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗