Biomedical subjects

T Neumann

Publications and source records attributed to T Neumann.

At least 37 records · Page 2Linked to original sources

PubMed2003

[Acute hemodynamic effects of biventricular and left ventricular pacing in chronic pacemaker-dependent patients with advanced heart failure].

The beneficial hemodynamic effects of cardiac resynchronization in patients with intraventricular conduction delay have been demonstrated. The potential hemodynamic effects of cardiac resynchronization to compensate the pacing-induced left ventricular conduction delay in chronically paced heart failure patients are not as well established. The aim of the study was to evaluate the acute hemodynamic effects of biventricular and left ventricular pacing in chronically paced patients with advanced heart failure. Fourteen consecutive pacemaker or defibrillator patients with permanent atrial fibrillation and AV block (11 male, 3 woman, mean age: 68 +/- 7 years) were enrolled in this study. There were 5 ischemic (36%) and 9 nonischemic (64%) patients (mean left ventricular ejection fraction: 19 +/- 5%; mean end-diastolic left ventricular diameter: 71 +/- 11 mm). In all patients a right ventricular and left ventricular (via coronary sinus) pacing lead was placed. The aortic and left ventricular hemodynamic measurements were performed using a two-channel micro-tip catheter. The measurements of the aortic pulse pressure (APP) and (dP/ dtmax) were performed during right ventricular apical pacing (RVP), left ventricular (LVP), and biventricular pacing (BVP) (70 bpm). Compared to RVP, LVP and BVP increased APP and dP/dtmax (35.8 +/- 4.2 vs 43.3 +/- 4.5 and 41.2 +/- 4 mmHg; p < 0.001) and (758 +/- 56 vs 967 +/- 60 and 961 +/- 62 mmHg/s; p < 0.001). LVP and BVP showed a comparable hemodynamic response. The hemodynamic effects were not related to the width of the paced QRS complex. Every patient showed improved hemodynamics during LVP and BVP unrelated to the underlying heart disease and to the baseline level of left ventricular dysfunction. BVP and LVP pacing acutely improve contractile left ventricular function in chronically paced patients with advanced heart failure.

Aged↗

PubMed2003

Comparison of generic health survey SF-36 and arrhythmia related symptom severity check list in relation to post-therapy AF recurrence.

AIM: The effect of applied therapy on quality of life (QoL) in patients with atrial fibrillation (AF) was investigated in recent studies. However, no information on clinical relevance of QoL assessing instruments in relation to post-ablation recurrence of AF is currently available. The aim of this study was to evaluate the clinical relevance of SF-36 and Arrhythmia Related Symptom Severity Check List (SSCL) to post-procedure AF recurrences in patients with paroxysmal AF undergoing pulmonary vein isolation (PVI). METHODS AND RESULTS: Sixty consecutive patients with AF were enroled in the study. The QoL was measured using SF-36 scale and SSCL. The questionnaires were administered at baseline then 3, 6, 9 and 12 months after the procedure. In order to define statistical power in relation to AF recurrence the scores were dichotomized. Positive and negative predictive accuracy (PPA, NPA) and test efficiency (sum of PPA and NPA) were calculated. Twenty-one out of 60 patients experienced a total of 66 recurrences of AF during follow-up. The parameters of SF-36 provided maximum test efficiency of 1.36, whereas the test efficiency of SSCL was 1.79. CONCLUSION: We conclude that SSCL is more specific instrument for a measurement of PVI success or failure.

Atrial Fibrillation↗

PubMed2002

Tissue response to microfibers of different polymers: polyester, polyethylene, polylactic acid, and polyurethane.

Tissue response to single polymer microfibers of polyester (PET), polyethylene (PE), poly(L-lactic acid) (PLA), and polyurethane (PU) was assessed using a rat subcutaneous model. Fibers of diameters ranging from 1 to 15 microm were aligned parallel to each other on polycarbonate frames and implanted in the subcutaneous dorsum in the subscapular region. After 5 weeks of implantation, fibrous capsule thickness was significantly less for fibers of diameters 1-5 than for those of 11-15 microm for all polymers tested. For PET and PU, 75.0 and 71.4% respectively of the 1-5 microm fibers had no capsule, while for PE and PLA only 45.5 and 56.3% respectively had no capsule. For 1-5 microm fibers, PE had significantly thicker capsules than PET and PU. Reducing fiber diameters from 6-10 to 1-5 microm induced a greater reduction in capsule thickness than changing polymers among PET, PE, and PLA. PU showed the least encapsulation of all polymers, demonstrating significantly thinner capsules than PET, PE, and PLA for 6-10 and 11-15 microm fibers.

Animals↗

PubMed2002

[Cooled tip ablation of left ventricular outflow tract tachycardia through the aortic sinus of valsalva].

BACKGROUND: Monomorphic tachycardia with an epicardial site of the arrhythmic focus in the left ventricular outflow tract (LVOT) usually cannot be ablated by an endocardial approach. We describe the use of cooled tip catheter ablation through the aortic sinus of valsalva to treat LVOT tachycardia. METHODS: In seven patients (four males, one with valvular cardiomyopathy, six patients without heart disease) with sustained and non-sustained ventricular tachycardia (VT) an epicardial focus of LVOT tachycardia could be identified by pace-mapping and earliest local activation within the aortic sinus of valsalva. Coronary angiography served to define the position of the coronary arteries with respect to the ablation catheter. High frequency current was delivered using a closed-loop cooled tip catheter system (Chilli Cool(R), Boston Scientific). ECG, Holter-ECG, echocardiography and transesophageal echocardiography were performed after the procedure and 3 months later. RESULTS: Foci were located in the left (two patients), in the right (three) and in the a coronary aortic sinus (two). Successful ablation could be achieved in six patients. No procedure-related complications could be observed during a mean follow-up of 4.2 months. CONCLUSION: Monomorphic VT with epicardial origin in the LVOT can be successfully treated by cooled tip ablation through the aortic sinus of valsalva. The use of a cooled tip ablation system may be favourable in several ways: 1) it allows the creation of deep lesions necessary to reach remote foci; 2) due to lower temperatures at the catheter/tissue interface surface tissue damage may be reduced; 3) lower catheter temperature may additionally reduce the risk of local clot formation which is crucial for all left-sided procedures and especially for ablation in the sinus of valsalva.

Adult↗

PubMed2002

[Atherosclerosis in HIV-positive patients].

Worldwide, human immunodeficiency virus (HIV) infection is one of the main health subjects. Even, the human immunodeficiency virus primarily effects the immune system, HIV infection also has an impact on other organs. Cardiovascular manifestations in HIV-infected patients could occur by the HI-virus itself or by opportunistic infections. Reports of myocardial infarction in young HIV-infected patients, who received protease inhibitors, have raised concerns about premature arteriosclerosis and coronary artery disease in this population. In the pre-protease inhibitor era, autopsy reports were the first to describe an association between coronary artery disease and HIV infection. Long-term antiretroviral therapy, including protease inhibitors, significantly reduced mortality, morbidity and revolutionized the care of HIV-infected patients. However, class-specific metabolic side effects, such as elevated total cholesterol and triglyceride levels and insulin resistance, have been described. These metabolic alterations of antiretroviral therapy impair the cardiovascular risk profile of HIV-infected patients. Even epidemiological studies found no significant effect of antiretroviral treatment type on coronary heart disease or myocardial infarction, an increase of arteriosclerosis in HIV-infected patients is suspected. Recent results of autopsy studies and analyses of endothelial function in patients with HIV infection described an effect of HIV and antiretroviral therapy on premature arteriosclerosis. The present article gives an overview about arteriosclerosis and coronary events in HIV-infected patients and the impact of antiretroviral therapy.

Antiretroviral Therapy, Highly Active↗

PubMed2002

[Evaluation of myocardial viability with contrast-enhanced magnetic resonance imaging--comparison of the late enhancement technique with positronemission tomography].

PURPOSE: To compare contrast-enhanced magnetic resonance imaging (MRI) and positron emission tomography (PET) in the evaluation of myocardial viability. METHODS: [ (18)F]-FDG-PET, [ (201)Tl]-TlCl-SPECT and contrast-enhanced MRI were performed in 29 patients with proven coronary artery disease and impaired left ventricular function to assess myocardial viability. MRI scans were done on a 1.5 T scanner (Magnetom Sonata, Siemens, Germany). After the steady-state free precession cine study, 0.2 mmol/kg BW of Gd-DPTA (Magnevist(R), Schering, Germany) were administered i. v. For the detection of "late enhancement" (LE) indicating scar, left ventricular long axes and contiguous short axis slices of 8 mm thickness were scanned using an inversion recovery turbo gradient echo sequence (TR 8.0 ms; TE 4.0 ms; TI 180 - 240 ms; FA 20 degrees ). The evaluation of LE and FDG uptake in PET with perfusion defect in SPECT was done using an 8 (basal, mid) and 4 (apical) segment model in all short axes to cover the entire ventricle. The transmural extent of LE was assessed using a 4-point score system. Comparison between the two modalities was performed on a segmental basis. RESULTS: A total of 1753 segments were assessed. In MRI, 40 % of the segments showed myocardial scar, whereas PET revealed impaired uptake in 25 %. MRI obtained a very low interobserver variability in detecting myocardial scar (kappa 0.92). Using PET as the standard of reference in the segmental comparison, contrast-enhanced MRI yielded a sensitivity of 84 % and a specificity of 76 % for the detection of scar. 18 % of all segments showed LE but normal FDG uptake, 83 % of them referred to subendocardial scars. CONCLUSIONS: There is close agreement between contrast-enhanced MRI and PET in detecting transmural myocardial scars. Superior spatial resolution enables MRI to detect and quantify even subendocardial scar. Therefore, larger studies using functional recovery after revascularisation as an endpoint have to prove whether MRI might replace PET as the standard of reference in the assessment of myocardial viability.

Aged↗

PubMed2002

Paracardial lipodystrophy versus pericardial effusion in HIV positive patients.

OBJECTIVE: To present an epicardial manifestation of the lipodystrophy syndrome, a side effect of antiretroviral treatment in HIV positive patients, which illustrates the important danger of false diagnosis. PATIENT: A 52 year old man with HIV (stage C3), diagnosed 10 years previously, was being treated with a combination of nelfinavir, nevirapine, and stavudine. Echocardiographic examination showed a low echogenic pericardial space that had increased from 4 mm to 18 mm over a 10 month period. The diagnosis of paracardial adipose tissue was verified by magnetic resonance tomography. Doppler echocardiographic parameters were not significantly altered (ratio of early to late ventricular filling 0.88 v 0.73, Tei index 0.30 v 0.36). CONCLUSION: Even a pericardial manifestation of lipodystrophy causes negligible functional impairment, misinterpretation of the lipodystrophy as a pericardial effusion and a subsequent puncture can have serious complications. Hence, it is strongly suggested that further differential diagnosis be used for HIV positive patients with an echocardiographic suspicion of pericardial effusion. Differential diagnosis by magnetic resonance tomography is possible.

Diagnosis, Differential↗

PubMed2002

Preoperative evaluation of chronic alcoholics assessed for surgery of the upper digestive tract.

BACKGROUND: Alcoholics are at risk of developing major complications in the postoperative period. Adequate prophylactic treatment, as well as preoperative abstinence, can significantly decrease the rate of complications. However, the preoperative diagnosis of alcoholism is difficult to establish. The purpose of this study was to assess whether three preoperative visits, an alcohol-related questionnaire (CAGE), and the laboratory markers carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GGT) would increase the rate of detection of chronic alcoholics. METHODS: The study included the Departments of ENT, Facial and Maxillofacial Surgery, and General Surgery of a university hospital; 705 male patients were assessed for tumor surgery of the upper digestive tract and were allocated to 5 different groups. All patients were seen three times, and five different strategies were used to detect chronic alcoholics. The gold standard was the diagnosis of alcohol misuse made by an experienced (blinded) investigator according to the DSM-III-R. The main outcome measurements were the detection rates of the different test strategies. RESULTS: By clinical routine alone, only 16% were detected during the first visit and 34% after three visits. If the CAGE questionnaire was added, sensitivity increased to 64%. The further addition of GGT or CDT led to 80 and 85% detections, respectively. A combination of all tests had a sensitivity of 91%. CONCLUSIONS: To detect more alcoholic patients at risk for major complications, patients should be seen more often, and additional diagnostic tools such as the CAGE, CDT, and GGT should be used before surgery.

Adult↗

PubMed2001

The coatomer-interacting protein Dsl1p is required for Golgi-to-endoplasmic reticulum retrieval in yeast.

Sec22p is an endoplasmic reticulum (ER)-Golgi v-SNARE protein whose retrieval from the Golgi compartment to the endoplasmic reticulum (ER) is mediated by COPI vesicles. Whether Sec22p exhibits its primary role at the ER or the Golgi apparatus is still a matter of debate. To determine the role of Sec22p in intracellular transport more precisely, we performed a synthetic lethality screen. We isolated mutant yeast strains in which SEC22 gene function, which in a wild type strain background is non-essential for cell viability, has become essential. In this way a novel temperature-sensitive mutant allele, dsl1-22, of the essential gene DSL1 was obtained. The dsl1-22 mutation causes severe defects in Golgi-to-ER retrieval of ER-resident SNARE proteins and integral membrane proteins harboring a C-terminal KKXX retrieval motif, as well as of the soluble ER protein BiP/Kar2p, which utilizes the HDEL receptor, Erd2p, for its recycling to the ER. DSL1 interacts genetically with mutations that affect components of the Golgi-to-ER recycling machinery, namely sec20-1, tip20-5, and COPI-encoding genes. Furthermore, we demonstrate that Dsl1p is a peripheral membrane protein, which in vitro specifically binds to coatomer, the major component of the protein coat of COPI vesicles.

Alleles↗

PubMed2001

Olfactory receptor-gene clusters, genomic-inversion polymorphisms, and common chromosome rearrangements.

The olfactory receptor (OR)-gene superfamily is the largest in the mammalian genome. Several of the human OR genes appear in clusters with > or = 10 members located on almost all human chromosomes, and some chromosomes contain more than one cluster. We demonstrate, by experimental and in silico data, that unequal crossovers between two OR gene clusters in 8p are responsible for the formation of three recurrent chromosome macrorearrangements and a submicroscopic inversion polymorphism. The first two macrorearrangements are the inverted duplication of 8p, inv dup(8p), which is associated with a distinct phenotype, and a supernumerary marker chromosome, +der(8)(8p23.1pter), which is also a recurrent rearrangement and is associated with minor anomalies. We demonstrate that it is the reciprocal of the inv dup(8p). The third macrorearrangment is a recurrent 8p23 interstitial deletion associated with heart defect. Since inv dup(8p)s originate consistently in maternal meiosis, we investigated the maternal chromosomes 8 in eight mothers of subjects with inv dup(8p) and in the mother of one subject with +der(8), by means of probes included between the two 8p-OR gene clusters. All the mothers were heterozygous for an 8p submicroscopic inversion that was delimited by the 8p-OR gene clusters and was present, in heterozygous state, in 26% of a population of European descent. Thus, inversion heterozygosity may cause susceptibility to unequal recombination, leading to the formation of the inv dup(8p) or to its reciprocal product, the +der(8p). After the Yp inversion polymorphism, which is the preferential background for the PRKX/PRKY translocation in XX males and XY females, the OR-8p inversion is the second genomic polymorphism that confers susceptibility to the formation of common chromosome rearrangements. Accordingly, it may be possible to develop a profile of the individual risk of having progeny with chromosome rearrangements.

Chromosome Breakage↗

PubMed2001

Linear and non-linear dynamics of heart rate variability in brain dead organ donors.

Recent studies outlined linear and non-linear dynamics in heart rate variability; however, their physiological origin is still unknown. The present study investigated the impact of cerebral function on linear and non-linear dynamics in heart rate variability. Electrocardiograms from seven brain dead organ donors and seven healthy volunteers were analyzed. Atropine was used in healthy volunteers to adjust their heart rate to that of the donors. As compared to healthy volunteers without atropine, the linear dynamics of heart rate variability, determined by time and frequency domain analyses, were significantly reduced in healthy volunteers with atropine and, to an even greater extent, in donors. Atropine tended to increase the complexity and non-linearity of heart rate variability in healthy volunteers, as determined by the correlation dimension D and the largest Lyapunov exponent L, respectively (D = 9.43 +/- 2.93 vs. 7.65 +/- 0.97 and L = 0.525 +/- 0.099 vs. 0.504 +/- 0.047 bits.beat-1; both NS), while these indices were significantly reduced in donors by 19.5 +/- 12.8% and 15.0 +/- 11.7%, respectively (D = 6.16 +/- 0.98 and L = 0.428 +/- 0.059 bits.beat-1; both p < 0.05 vs. volunteers). Thus, loss of cerebral function reduces both linear and non-linear components of heart rate variability.

Adult↗

PubMed2001

Spatial impact of the Oder river plume on water quality along the south-western Baltic coast.

The Oder (Odra) river is the most important nutrient source and pollutant for the south-western Baltic Sea. Adjacent German-Polish coastal waters, the Oder (Szczecin) Lagoon and the Oder (Pomeranian) Bight therefore suffer from severe eutrophication and water quality problems. At the same time, summer (bathing) tourism is the most important economical factor in this coastal zone, especially on the islands of Usedom and Wolin. On the basis of model simulations and remote sensing data we analysed the spatial extent and variability of the Oder river plume in the lagoon and the Balic Sea in common summer situations and during the extreme Oder flood in August 1997. Water quality shows pronounced gradients between coastal waters and open Baltic Sea. In the lagoon, it usually takes more than 6 weeks until Oder water enters the large western bay, the Kleines Haff. During transport, degradation, transformation and sedimentation processes alter the water quality and prevent the inner coast of Usedom from direct impact of polluted Oder water. Ongoing nutrient supply promotes intensive algal proliferation in all parts of the lagoon and contributes to the low water transparency. Oder water passing the lagoon and entering the Baltic Sea is transported over long distances in narrow bands along the shore. Under easterly winds the water quality near well-known spas on Usedom is reduced due to Oder river plume impact. Upwelling effects can have negative impact on water quality, too. Intensive blooms of potentially toxic blue-green algae species, are the rule in the lagoon and frequent in the Oder Bight in summer. They are a hazard and limit the acceptance of swimming beaches at the inner coast of Usedom. Practical consequences of variable water quality gradients e.g. on hygienic water sampling are discussed.

Baltic States↗

PubMed2001

Minimal protection of the liver by ischemic preconditioning in pigs.

Ischemic preconditioning (IP) protects the rat liver. In pigs, in which hepatic tolerance to ischemia is similar to that in humans, information on IP is lacking. Therefore, in enflurane-anesthetized pigs, hepatic vessels were occluded for 120 min (protocol 1) or 200 min (protocol 2) without (control) and with IP (3 times 10 min ischemia-reperfusion each). In protocol 1, cumulative bile flow (CBF) during reperfusion was greater in IP (47.3 +/- 5.2 ml/8 h) than in control (17.1 +/- 7.8 ml/8 h, P < 0.05). ATP content tended to recover toward normal during reperfusion in IP, whereas it remained at ischemic levels in control. Serum enzyme concentrations increased similarly during reperfusion, and <1% hepatocytes were necrotic or stained terminal deosynucleotidyl transferase-mediated dUTP nick-end labeling-positive in control and IP groups. In protocol 2, no differences in CBF, ATP, or serum enzyme concentrations during reperfusion were measured between control and IP groups, except for a somewhat reduced lactate dehydrogenase in IP. The number of necrotic or terminal deosynucleotidyl transferase-mediated dUTP nick-end labeling-positive hepatocytes tended to be greater in the IP than the control group. Thus IP provides some functional protection against reversible ischemia but no protection during prolonged ischemia in pigs.

Adenosine Triphosphate↗

PubMed2001

Progressive loss of perfusion-contraction matching during sustained moderate ischemia in pigs.

It is unclear whether perfusion-contraction matching (PCM) is maintained during prolonged myocardial ischemia. In 27 anesthetized pigs, left anterior descending coronary arterial inflow was reduced to decrease an anterior work index (WI) at 5 min of hypoperfusion by 40% and then maintained at this level for 12 or 24 h. With 12 h of hypoperfusion, the myocardium remained viable in 6 of 7 pigs (with triphenyltetrazolium chloride; TTC) and with 24 h of hypoperfusion in 5 of 11 pigs (TTC, histology). The reduction in WI to 62 +/- 4 and 62 +/- 3% of baseline in the two groups was matched to the reduction of transmural blood flow (TBF; microspheres) at 5 min of hypoperfusion, averaging 59 +/- 4 and 60 +/- 2% of baseline. With prolonged hypoperfusion, WI decreased to 30 +/- 5% at 12 h and 18 +/- 3% at 24 h; TBF remained unchanged (53 +/- 4 and 54 +/- 4%). The added calcium concentration required for the half-maximal increase in WI increased from 121 +/- 25 microg/ml blood at baseline to 192 +/- 26 microg/ml blood at 12 h of hypoperfusion. Thus, with hypoperfusion for 24 h, PCM is progressively lost, and calcium responsiveness is reduced.

Animals↗

PubMed2001

Determination of the net exchange rate of tubulin dimer in steady-state microtubules by fluorescence correlation spectroscopy.

The microtubule cytoskeleton plays an important role in eukaryotic cells, e. g., in cell movement or morphogenesis. Microtubules, formed by assembly of tubulin dimers, are dynamic polymers changing randomly between periods of growing and shortening, a property known as dynamic instability. Another process characterizing the dynamic behaviour is the so-called treadmilling due to different binding constants of tubulin at both microtubule ends. In this study, we used tetramethylrhodamine (TMR)-labeled tubulin added to microtubule suspensions to determine the net exchange rate (NER) of tubulin dimers by fluorescence correlation spectroscopy (FCS) as a measure for microtubule dynamics. This approach, which seems to be suitable as a screening system to detect compounds influencing the NER of tubulin dimers into microtubules at steady-state, showed that taxol, nocodazole, colchicine, and vinblastine affect microtubule dynamics at concentrations as low as 10(-9)-10(-10) M.

Animals↗

PubMed2001

Coupling biology and oceanography in models.

The dynamics of marine ecosystems, i.e. the changes of observable chemical-biological quantities in space and time, are driven by biological and physical processes. Predictions of future developments of marine systems need a theoretical framework, i.e. models, solidly based on research and understanding of the different processes involved. The natural way to describe marine systems theoretically seems to be the embedding of chemical-biological models into circulation models. However, while circulation models are relatively advanced the quantitative theoretical description of chemical-biological processes lags behind. This paper discusses some of the approaches and problems in the development of consistent theories and indicates the beneficial potential of the coupling of marine biology and oceanography in models.

Animals↗

PubMed2000

Favorable remodeling enhances recovery of regional myocardial function in the weeks after infarction in ischemically preconditioned hearts.

BACKGROUND: In a previous study, we found that recovery of segment shortening in the ischemic zone of conscious, chronically instrumented rabbits was significantly better in ischemically preconditioned than control animals after 72 hours of reperfusion. However, although this period of reperfusion was felt to be sufficient to allow recovery from stunning, regional function was disproportionately low for the size of the infarcts. METHODS AND RESULTS: To further characterize the recovery of left ventricular regional function, rabbits were chronically instrumented with a balloon occluder around a branch of the left coronary artery and a pair of ultrasonic crystals to monitor segment shortening in the ischemic zone. The preconditioned group had 1 cycle of 5-minute occlusion/10-minute reperfusion before a 30-minute occlusion, whereas control rabbits experienced only the 30-minute occlusion. All monitored segments were either dyskinetic or akinetic during the 30-minute occlusion. There was no difference in function between the 2 groups until 24 hours of reperfusion. At 72 hours, systolic shortening in control hearts averaged only 5% of the preischemic value, whereas shortening was 29% of baseline in preconditioned hearts. By day 21, systolic shortening averaged 26% in control hearts and 65% in preconditioned hearts (P<0.02) and appeared to have reached a plateau. Infarct size was 31.4+/-2.8% and 15.5+/-2.1% in control and preconditioned hearts, respectively. Moreover, in ischemically preconditioned hearts, the recovery of regional function was better than in controls for any given amount of microinfarction in the myocardial segment between crystals (P=0.02). CONCLUSIONS: The progressive improvement in preconditioned hearts is most consistent with favorable remodeling in the ischemic zone, which the preconditioning process seems to accentuate.

Animals↗

PubMed2000

Limitation of infarct size in rabbit hearts by the novel adenosine receptor agonist AMP 579 administered at reperfusion.

The novel A(1)/A(2)adenosine receptor agonist AMP 579 has been reported to reduce myocardial infarct size in pig and dog. The present study tested the effect of AMP 579 in two rabbit models. In open-chest rabbits undergoing 30 min of regional ischemia and 3 h of reperfusion AMP 579 (3 microg/min/kg) reduced infarct size when treatment was started either 10 min before ischemia or 10 min prior to reperfusion from 36.4+/-3.1% of the risk zone in untreated hearts to 11.8+/-4.4 and 12.3+/-1.0%, respectively. To determine whether protection observed when the drug was administered shortly before reperfusion represented a long-lasting effect rather than merely a transient delay of necrosis, the chest wound was closed in layers and the rabbits permitted to recover. After 3 days the hearts were removed to evaluate infarct size. Continued limitation of infarct size after 3 days of reperfusion (8.2+/-2.8% of the risk zone) confirmed that sustained tissue salvage had been conferred by the drug. In isolated, buffer-perfused rabbit hearts undergoing 30 min of regional ischemia and 2 h of reperfusion, AMP 579 again limited infarct size (8.6+/-2.9% of the risk zone) when treatment started 10 min prior to reperfusion, arguing against an anti-leukocyte mechanism of protection. AMP 579's protective effect in this in vitro model was abrogated by 8-(p-sulfophenyl)theophylline, indicating that it was mediated through adenosine receptors. We conclude that AMP 579 given just prior to reperfusion may be an effective anti-infarct intervention.

Animals↗