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Biomedical subjects

S Häggmark

Publications and source records attributed to S Häggmark.

At least 37 records · Page 2Linked to original sources
PubMed1997

Clinical effects of the heparin coated surface in cardiopulmonary bypass.

OBJECTIVE: In a randomised study of 120 patients, undergoing primary operation for coronary heart decease, two groups were investigated as regards to the effects of heparin coated cardiopulmonary bypass on brain function parameters and general clinical outcome. The study group (n = 56) was perfused using an extra-corporeal circuit treated with covalent bonded heparin; the control group (n = 59) used an identical set-up without heparin treatment. Systemic heparin doses were calculated to achieve ACT levels of 250 and 500 s, respectively. Postoperative course was evaluated by examining a set of clinically relevant parameters including a detailed registry of postoperative deviations. Brain function was assessed by the biochemical marker S-100 and tests of memory performance. RESULTS: There were several signs of reduced operative trauma in the study group. Hospital stay was reduced by nearly 1 day (P < 0.05). Time on postoperative ventilatory support was approximately 4 h shorter (P = 0.009). Chest drain blood loss was decreased both at 8 (P = 0.01) and 24 h (P = 0.007) postoperatively. Body temperature was lower after surgery and especially on days 2 (P = 0.03) and 3 (P = 0.01). Perioperative creatinine elevation was significantly reduced (P = 0.03). Neurological deviations were fewer (P = 0.01). Brain function assessment revealed reduced plasma levels of S-100 both at termination of cardiopulmonary bypass (P = 0.008) and 7 h later (P = 0.04). However, no remediation of memory impairment could be demonstrated. CONCLUSIONS: Cardiopulmonary bypass with covalent bonded heparin attached to the extra-corporeal circuit in combination with a reduced systemic heparin dose seems to reduce safely and effectively the operative stress to the patient. There were also signs of improved cerebral protection.

Anticoagulants↗
PubMed1997

Aortic cross-clamping influences regional net release and uptake rates of tissue-type plasminogen activator in pigs.

BACKGROUND: The key regulator of intravascular fibrinolysis, tissue-type plasminogen activator (t-PA), is released from a dynamic endothelial storage pool. The aim of the study was to investigate regional t-PA net release and uptake rates in response to infra-renal aortic cross-clamping (AXC) and declamping (DC). METHODS: Anesthetized pigs were studied during 5 min of AXC, followed by a 35-min declamping (DC) period. Arterio-venous concentration gradients of total and active t-PA, as well as respective plasma flows, were simultaneously obtained across the preportal, hepatic, coronary and pulmonary vascular beds. Plasma levels of total t-PA (ELISA with purified porcine t-PA as standard), and active t-PA (spectrophotometric functional assay) were determined. RESULTS: Prior to AXC, we found a high net release rate of total t-PA across the preportal vascular bed (1700 ng.min-1 P < 0.001), and a high hepatic net uptake (4900 ng.min-1, P < 0.001), while coronary and pulmonary t-PA net fluxes were small and variable. AXC per se did not induce significant alterations in net fluxes of t-PA. Following DC, preportal and coronary net releases of total t-PA increased (to 2900 ng.min-1 and 60 ng.min-1, respectively). Despite an increase in hepatic net uptake of total t-PA (to 6100 ng.min-1) after DC, a significant increase in hepatic venous total t-PA occurred. CONCLUSIONS: The release and uptake of t-PA is indicated to be dynamic and organ-specific. DC induces an acute profibrinolytic reaction in preportal organs. The high hepatic t-PA uptake capacity restricts preportal profibrinolytic events to affect the systemic circulation.

Anesthesia↗
PubMed1997

The relative safety of an oxygenator.

Analysis of prospectively registered incidents related to cardiopulmonary bypass (CPB) was initiated to establish the incident rate for 10 different oxygenator brands employed over a seven-year period in 5000 clinical perfusions. A general safety index (SI) was defined as the number of recorded incidents in a given series of oxygenators divided by its total number and multiplied by 100. Specific SI was calculated for each of the following categories: high-pressure drop, debris, gas exchange, leakage, material failure and oxygenator change-out. An SI of 0.2 was arbitrarily set as a reference and an acceptable safety level. An estimate of the relative risk for a particular oxygenator brand was compared with the reference by calculating the odd's ratio with a 95% confidence interval. The mean SI was determined to be 1.6, ranging from 0 for the Maxima CBAS and the Cobe CML to 2.92 for the Safe oxygenator. The dominating specific type of incident was HPD with an SI of 0.81 followed by debris, SI = 0.71. A systematic analysis of adverse events in CPB may be used to evaluate and to set standards, a method already employed in the pharmaceutical industry. Our results indicate that oxygenator safety margins may vary between different brands.

Cardiopulmonary Bypass↗
PubMed1994

Anaesthesia for abdominal vascular surgery in patients with coronary artery disease (CAD), Part I: Isoflurane produces dose-dependent coronary vasodilation.

The effects of anaesthesia for major abdominal vascular surgery on coronary flow regulation and mechanisms of myocardial ischaemia were studied in 56 patients with CAD, using a randomized, partly double-blinded protocol. After induction with fentanyl (3 micrograms.kg-1) and thiopentone (2-4 mg.kg-1) and tracheal intubation, principal anaesthetics were nitrous oxide/oxygen (60/40) with isoflurane (n = 20), halothane (n = 19) or fentanyl (15-20 micrograms.kg-1) (n = 17). Conventional invasive techniques and coronary venous retrograde thermodilution were used to assess systemic and coronary haemodynamics. Coronary vascular resistance was estimated from myocardial oxygen extraction. Myocardial ischaemia was diagnosed by 12-lead ECG and/or anterior wall motion abnormalities by cardiokymography and/or myocardial lactate production. When adjustment of anaesthetic dose was insufficient for haemodynamic control, i.v. phenylephrine and nitroglycerine were administered to treat hypotension and hypertension or cardiac failure respectively. Measurements were performed at four specific intervals; awake, before surgery and 10 and 30 min after abdominal incision. Comparable changes of systemic haemodynamics and myocardial oxygen consumption were observed in the three groups. Coronary vasodilation was evidenced in isoflurane patients only and was linearly dose-dependent (P < 0.001). Partial Least Squares Projections to Latent Structures modelling with cross validation confirmed this dose-dependency and ruled out a clinically measurable influence by intervention drugs or simultaneous systemic haemodynamic abnormalities. The incidence of myocardial ischaemia during anaesthesia and surgery was comparable in the three groups (35, 37 and 24%, respectively) and there was an association with systemic haemodynamic aberrations in 19 of the 27 ischaemic episodes. In contrast to ischaemic halothane and fentanyl patients, isoflurane patients with ischaemia had significantly lower myocardial oxygen extraction (P = 0.008 and P = 0.001, respectively), indicating that the oxygen extraction reserve was not utilized in a normal way during ischaemia.

Abdomen↗
PubMed1994

Anaesthesia for abdominal aortic surgery in patients with coronary artery disease, Part II: Effects of nitrous oxide on systemic and coronary haemodynamics, regional ventricular function and incidence of myocardial ischaemia.

This study examines the effects of nitrous oxide on haemodynamics, anterior left ventricular (LV) function and incidence of myocardial ischaemia in abdominal vascular surgical patients with coronary artery disease. Forty-seven patients were randomly assigned to isoflurane-fentanyl anaesthesia with nitrous oxide-oxygen vs air-oxygen (control). Systemic and coronary haemodynamics, 12-lead ECG, LV anterior wall motion by cardiokymography (CKG) and myocardial lactate balance were recorded at four intervals: before and during anaesthesia and 10 and 30 minutes into surgery. Systemic haemodynamics were controlled by anaesthetic dose, and, when insufficient, by i.v. nitroglycerine (NG) in case of LV failure (PCWP > 18 mmHg) and by phenylephrine during hypotension. We found that nitrous oxide was associated with greater need for i.v. nitroglycerin (patients: P = 0.031, episodes P = 0.005) and more myocardial ischaemia (patients P = 0.012, episodes P = 0.001) despite systemic and coronary haemodynamics comparable to the control group. We conclude that nitrous oxide, known to have both sympathomimetic and cardiodepressive actions, produced cardiodepression in the face of sympathetic stimulation. Our study design did not allow to conclude if myocardial ischaemia was the consequence of increased wall stress or a reason for the observed LV dysfunction. The higher incidence of introperative myocardial ischaemia and need for NG did not cause increased cardiac morbidity.

Abdomen↗
PubMed1994

Clinical evaluation of the CDI System 400 blood gas monitor.

The CDI 400 blood gas monitor was evaluated by investigating its clinical performance in 30 patients undergoing cardiac surgery requiring cardiopulmonary bypass. Arterial and venous blood samples were withdrawn during stable hypothermic conditions. Reference analysis was performed on the ABL4 blood gas analyzer. A total of 229 samples were included for calculations of bias and precision. Simple regression analysis was utilized to illustrate the relationship between the tested monitor and its reference. Results revealed an acceptable agreement for pH and arterial pO2 measurements. Venous pO2 bias and precision were poor (+0.76 +/- 1.07 kPa). Arterial and venous pCO2 were generally overestimated (+0.5 +/- 0.4 kPa and +0.2 +/- 0.4 kPa). Performance given as correlation coefficients indicated a similar pattern. Slopes and intercepts deviated from the line of identity for all parameters analysed. In summary: the CDI 400 is a valid instrument in guiding the perfusionist with crucial trend information. However, its general performance implies that a reference blood gas analyser is still needed.

Aged↗
PubMed1994

Continuous venous oximetry: a comparative study between the CDI 100 and the Bentley OxySat II.

Two in-line oxygen saturation monitors, the CDI 100 and OxySat II, were evaluated in the clinical setting. Eighty-seven venous blood samples were drawn during 20 elective cardiopulmonary bypass procedures. Monitor readings were compared to OSM III co-oximeter values. The results revealed that saturation (%) determination was biased, -3.16 +/- 2.21 SD for the CDI 100 and -0.34 +/- 2.17 SD for the OxySat II. Hemoglobin (g/dl) and hematocrit (%) measurement, available only for the CDI 100, resulted in a bias of +5.54 +/- 5.68 SD and +1.94 +/- 1.78 SD, respectively. It was concluded that both monitors operated within clinically acceptable limits, with a more favorable outcome for the OxySat II.

Aged↗
PubMed1993

Quantification of myocardium at risk and detection of reperfusion by dynamic vectorcardiographic ST segment monitoring in a pig occlusion-reperfusion model.

OBJECTIVE: The aim was to investigate whether continuous computerized vectorcardiographic monitoring of absolute spatial ST vector magnitude (ST-VM) and spatial ST change vector magnitude (STC-VM) during coronary occlusion could be used to estimate the size of myocardium at risk; and also to test whether reperfusion could be distinguished from sustained occlusion by continuous monitoring of ST vector alterations. METHODS: Computerised vectorcardiographic monitoring via Frank leads was applied in a closed chest occlusion-reperfusion pig model. Coronary occlusion over 24 h was produced in 20 animals by injecting a 2 mm ball into the left anterior descending coronary artery (n = 7), the right coronary artery (n = 8), and the left circumflex coronary artery (n = 5). Another 31 pigs were reperfused by retraction of the ball after 30 (n = 10), 60 (n = 15), or 90 (n = 6) min of left anterior descending artery occlusion. The extent of the myocardium at risk was measured by autoradiography. RESULTS: Seven animals were excluded. Irrespective of occluded coronary artery the relative parameters STC-VM over the first 30 min of occlusion correlated closely with area at risk, that is, the mean STC-VM between 10 and 30 min of occlusion (r = 0.78 p < 0.001). The absolute parameter ST vector magnitude (ST-VM) did not reflect ischaemia in 16/44 animals and did not correlate significantly with area at risk. The weight of myocardium at risk (MAR) was predictable from STC-VM: MAR weight (measured) = 0.97 x MAR weight (predicted) + 0.26 (g), r = 0.81, p < 0.001. STC-VM decline rate, time to STC-VM plateau, and cumulated sum plots of STC-VM were all able to distinguish reliably between reperfused animals and those with permanent occlusion. A paradoxical increase in STC-VM - "reperfusion peak" - was detected in 17/31 (55%) of the animals. This phenomenon was related to large amount of myocardium at risk or to a long occlusion time. CONCLUSION: Dynamic vectorcardiographic ST monitoring provides adequate estimation of myocardium at risk and enables detection of reperfusion in experimental myocardial ischaemia.

Animals↗
PubMed1993

Ischaemia and reperfusion induced transient QRS vector changes: relationship to size of the ischaemic territory.

OBJECTIVE: The aim was to investigate QRS vector changes during the first 30 min of coronary occlusion or the early phase of reperfusion with special reference to location and size of myocardium at risk. METHODS: 24 h experiments were performed in closed chest anaesthetised pigs. QRS vectors were studied by computerised vectorcardiography via Frank leads. Occlusion of the left anterior descending coronary artery followed by reperfusion was induced in 23 pigs and a sustained occlusion in 20 pigs: left anterior descending coronary artery in seven, right coronary artery in eight, and left circumflex coronary artery in five. Myocardium at risk was measured in postmortem autoradiograms. Eight animals were excluded. RESULTS: Four minutes after occlusion, QRS(mean) deviated towards the ischaemic region in 34/35 animals and returned thereafter at varying speeds. In half of the reperfused animals, deviation of QRS vectors towards the ischaemic territory was also observed during the first minutes of reperfusion. A paradoxical increase in QRS vector changes, "reperfusion peak", was recorded during the initial minutes of reperfusion in 12/19 animals. Maximum spatial QRS vector magnitude increased in all right coronary or left circumflex coronary occlusion animals compared to 6/25 in left anterior descending coronary occlusion animals. QRS vector difference, change in spatial QRS vector angle, and maximum change in QRS azimuth 4 min after occlusion correlated significantly with extent of myocardium at risk. CONCLUSIONS: Marked directional and quantitative QRS vector changes, with significant relation to size and location of myocardium at risk, were recorded during the initial minutes of ischaemia. The transient increase in QRS vector changes during the first minutes of reperfusion deserves further exploration as a new indicator of reperfusion.

Animals↗
PubMed1992

Effects of reperfusion and superoxide dismutase on myocardial infarct size in a closed chest pig model.

OBJECTIVE: The aim was to study the effects on myocardial infarct size of reperfusion alone or of CuZn superoxide dismutase (SOD) as an adjunct to reperfusion. METHODS: Occlusion was induced in closed chest, pentobarbitone anaesthetised, mechanically ventilated pigs by injection of a 2 mm ball into a preselected coronary artery. Reperfusion was achieved by retraction of the ball via an attached filament. Twenty nine placebo treated and 25 SOD treated animals were subjected to 30 (n = 21), 60 (n = 21), and 90 (n = 12) min of coronary occlusion followed by reperfusion to 24 h; a control group of 24 pigs was subjected to a sustained occlusion for 24 h. Infarct size was assessed by tetrazolium staining and plasma creatine kinase (CK), aspartate aminotransferase (ASAT), and lactate dehydrogenase (LD). In the CuZn SOD group, 200 mg bovine CuZn SOD was given as a bolus intravenously immediately before reperfusion followed by a continuous infusion (100 mg) for 60 min. The size of the ischaemic myocardium at risk was measured from post mortem autoradiograms. RESULTS: Infarct size as percent of myocardium at risk was 46.0(SD 15.5)%, 80.1(9.9)%, and 88.9(5.0)% respectively in placebo animals with 30, 60, and 90 min occlusion, and 94.2(5.1)% in pigs with 24 h sustained occlusion. Compared to 24 h sustained occlusion, limitation of infarct size by reperfusion was only demonstrated in the 30 (p less than 0.001) and 60 min groups (p less than 0.001). Plasma values of CK, ASAT, and LD at 90 min post-reperfusion correlated closely with infarct size as assessed by tetrazolium staining and were related to occlusion duration. No myocardial salvage, as assessed by plasma ASAT, CK, or LD, was shown in the SOD treated groups. CONCLUSIONS: Early reperfusion resulted in myocardial salvage as assessed by tetrazolium staining and peak ASAT, CK, and LD at 90 min after the reperfusion. No limitation of infarct size by SOD could be demonstrated from analyses of plasma CK, ASAT, or LD.

Animals↗
PubMed1992

A closed-chest myocardial occlusion-reperfusion model in the pig: techniques, morbidity and mortality.

Extensive preparative surgery and lengthy experimentation may lead to high rate of complications and mortality in myocardial ischaemia studies. These problems are particularly common when pigs are used as the subject as they are prone to develop lethal ventricular arrhythmias. Here, a closed-chest model is presented, in which the trauma of major preparative surgery is avoided. One-hundred and twelve pentobarbital-anaesthetized, mechanically ventilated pigs were used. Coronary occlusion was produced by injection of a 2 mm diameter ball via a modified coronary angiography catheter. Reperfusion was induced by retraction of the ball via a thin filament attached to the ball. The amount of the myocardium at risk (MAR) was 8.23 +/- 2.41% (mean +/- SD) of the left plus right ventricular weight. It was possible to carry out scheduled 24 h experiments in 87 out of 93 animals (93.5%). Preparative mortality was 1.8% and 24 h mortality 6.5%. Ventricular fibrillation (VF) occurred during preparation in 3.6%, during coronary occlusion in 7.3% and during reperfusion in 5.0% of the animals. VF was significantly related to a large zone of MAR and insufficient premedication. Catheter- or ball-induced complications were found in 10.7%. Mortality and incidence of VF are considerably lower in this closed-chest model than in a previously reported open-chest pig preparation.

Animals↗
PubMed1990

Limitation of myocardial infarct size by superoxide dismutase as an adjunct to reperfusion after different durations of coronary occlusion in the pig.

Superoxide dismutase (SOD) has been documented to limit myocardial infarct size in the richly collateralized dog heart. This study was designed to explore this concept in a low-collateralized animal model. A blind, randomized, placebo-controlled protocol was used in 65 pentobarbital-anesthetized pigs subjected to closed-chest left anterior descending coronary artery occlusion for 30 (n = 22), 60 (n = 22), and 90 (n = 14) minutes followed by reperfusion up to 24 hours from the start of occlusion. Another seven control pigs were subjected to 24 hours of permanent occlusion. A total dose of 9 mg/kg bovine CuZn SOD was administered as a bolus injection immediately before reperfusion followed by a 1-hour infusion. Infarct size was assessed by tetrazolium staining. Myocardium at risk and collateral flow were determined by using cerium-141-labeled microspheres (15 microns) during the occlusion. After 30 minutes of occlusion, infarct sizes in placebo versus SOD-treated animals were 45.5 +/- 15.7% vs. 23.8 +/- 15.6% of myocardium at risk (p = 0.007). The corresponding values after 60 minutes of occlusion were 78.6 +/- 9.3% vs. 66.9 +/- 14.6% (p = 0.035). SOD administered after 90 minutes of occlusion did not limit infarct size (88.5 +/- 4.8% vs. 92.3 +/- 5.2%). Twenty-four hours of coronary occlusion resulted in infarction of 92.4 +/- 4.2% of myocardium at risk. (All values are mean +/- SD.) Ventricular fibrillation occurred in only nine pigs distributed equally between SOD and placebo. The results indicate that CuZn SOD has the potential to further improve the myocardial salvage established by reperfusion of an ischemic pig heart territory. However, the narrow time window for limiting infarct size in the pig by reperfusion is not much extended by SOD.

Animals↗
PubMed1990

Systemic, pulmonary and renal haemodynamic effects of large intravenous doses of high and low osmolar contrast media. An investigation in the pig of ratio 1.5 and ratio 3 media.

The central, peripheral and renal haemodynamic effects of intravenous infusion (1 ml/s) of large doses (4 ml/kg body weight) of non-ionic (iohexol) and ionic (metrizoate and ioxaglate) contrast media were studied in 24 anaesthetized pigs. All contrast media showed marked haemodynamic effects with an increase of mean right atrial pressure, mean pulmonary arterial pressure, mean pulmonary occlusion pressure, cardiac output and stroke volume. The response of the pulmonary circulation to contrast media was a fall rather than a rise in pulmonary vascular resistance. No significant changes were detected in the renal circulation after infusion of contrast media.

Animals↗
PubMed1989

Comparison of hemodynamic, electrocardiographic, mechanical, and metabolic indicators of intraoperative myocardial ischemia in vascular surgical patients with coronary artery disease.

To compare mechanical, electrocardiographic, and metabolic indices of myocardial ischemia, the cardiokymogram (CKG), the V5 ECG, left anterior descending coronary artery territory lactate extraction, and pulmonary capillary wedge pressure (PCWP) were measured in 53 vascular surgical patients with coronary artery disease. Measurements were performed preoperatively and at four specific intraanesthetic intervals: after tracheal intubation, before surgery, and 10 and 30 min after incision. Measurements and sampling sequence took 5-7 min, and therapy for the probable cause of ischemia was instituted following completion of this sequence. Myocardial ischemia was defined as type II or III CKG, 0.1 mV or greater horizontal or downsloping depression of V5 ECG ST segment, 0.2 mV or greater elevation of V5 ECG ST segment, or myocardial lactate production. Thirty-nine patients (74%) had a total of 89 episodes of myocardial ischemia. Seventy-four episodes (83%) were detected by the CKG, 31 (44%) were evident on the ECG, and 13 (15%) by evidence of lactate production. The concordance among the indices of myocardial ischemia was poor. Patients with an abnormal preoperative ECG experienced a greater number of ischemic episodes (P less than 0.001). Elevation of PCWP or the presence of A-C or V-waves greater than 5 mmHg above the mean did not individually reflect ischemia reliably. Intraoperative myocardial ischemia is common in vascular surgical patients and is most sensitively detected by ventricular wall motion abnormality.

Aged↗
PubMed1989

Cardiotoxicity of ropivacaine--a new amide local anaesthetic agent.

Anaesthetically equipotent doses of lidocaine, bupivacaine and a new bupivacaine-like local anaesthetic agent, ropivacaine, were injected into the left anterior descending coronary artery of pentobarbital-anaesthetized pigs. The aim was to study the cardiotoxicity of ropivacaine in relation to the two other drugs. A random, crossover, dose response study design was used. The following doses of the drugs were administered: lidocaine (L): 1,2,4,8 and 16 mg, bupivacaine (B): 0.25, 0.5, 1,2 and 4 mg and ropivacaine (R): 0.33, 0.66 1.33, 2.66 and 5.33 mg. Systemic haemodynamics, left ventricular dP/dT and a 12-lead electrocardiogram were recorded continuously during the study period. The drugs depressed cardiac contractility in relation to their local anaesthetic potency on the isolated nerve-4:3:1 (B:R:L). The prolongation of the ECG QRS-interval was regarded as a measure of electrophysiologic toxicity. Comparable prolongation of the QRS-interval was recorded after 2 mg of bupivacaine, 4.5 mg of ropivacaine and 30 mg of lidocaine. Thus, the electrophysiological toxicity ratio was 15:6.7:1 (B:R:L). Provided local anaesthetic potency data can be extrapolated from the isolated nerve preparation to regional anaesthesia in humans, ropivacaine appears to provide a greater margin of safety than bupivacaine, if inadvertently injected into the venous circulation.

Amides↗
PubMed1989

Anevac-D, a new system for close scavenging of anesthetic gases in dental practice.

Anevac-D, a new system for close scavenging of anesthetic gases in dental practice is described. It consists of a rubber nose mask surrounded by an outer rigid shell and a chin scavenger. A vacuum in the slot between the nose masks provides scavenging of gases escaping from the inner mask. Gases escaping from the mouth are evacuated mainly by the skin scavenger. The efficiency of this system was assessed in healthy volunteers using argon as a tracer gas. Mass spectrometry was used for measurement of inspired, expired, and scavenged gas concentrations. The scavenging efficiency of the complete system was around 80% and was not affected by poor patient cooperation. It decreased to about 65% when the chin scavenger was removed. The dentist's exposure was measured by sampling of argon in the breathing zone by a Saran system. The average 4-min exposure varied between 90 and 250 ppm depending on system configuration and patient cooperation. Patient acceptance and clinical applicability were judged good. It is concluded that the Anevac-D system provides excellent scavenging properties and exposure levels well within the official recommendations by the Swedish Board of Occupational Safety and Health.

Adolescent↗
PubMed1989

Pharmacokinetics and central haemodynamic effects of doxorubicin and 4'epi-doxorubicin in the pig.

The relationship between the cardiotoxicity and the haemodynamics/pharmacokinetics of clinical concentrations of doxorubicin and 4'epi-doxorubicin was studied. Twelve pigs were randomized to receive i.v. infusions of either drug of 50 mg/m2 over 3.0 min. Aortic, pulmonary arterial, coronary sinus and central venous plasma concentrations of the agents were determined until 180 min after the infusion. The V5 ECG, left ventricular dP/dT, aortic, pulmonary arterial and right atrial pressures were recorded continuously, cardiac output and coronary sinus blood flow were recorded intermittently. No haemodynamic changes were recorded after administration of either drug. Pharmacokinetic data indicated myocardial extraction, followed by myocardial release of both drugs. This release was higher after administration of 4'epi-doxorubicin than after doxorubicin, within the range 2-4 min and 20-40 min after the infusion. The tendency of greater myocardial release of 4'epi-doxorubicin may explain its lower cardiotoxicity.

Animals↗