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Biomedical subjects

B Bauer

Publications and source records attributed to B Bauer.

At least 145 records · Page 8Linked to original sources
PubMed1993

Short report: ramipril and hydrochlorothiazide combination therapy in hypertension: a clinical trial of factorial design. The East Germany Collaborative Trial Group.

OBJECTIVE: To identify appropriate dosages of ramipril and hydrochlorothiazide (HCT) when given in combination once a day for the treatment of essential hypertension. DESIGN: A 2- or 4-week placebo run-in followed by 6-week, double-blind, parallel-group phase: 4 x 3 factorial (2.5, 5 and 10 mg ramipril; 12.5 and 25 mg HCT; all six combinations; placebo). SETTING: Office practice (21 centres). PATIENTS AND PARTICIPANTS: Patients with mild-to-moderate essential hypertension (World Health Organization stage I-II; supine diastolic blood pressure 100-115 mmHg in last 2 weeks of run-in): 581 enrolled, 534 randomly assigned to double-blind therapy and 517 completed. MAIN OUTCOME MEASURES: Reduction in supine and standing blood pressure. RESULTS: In pairwise comparisons, the combinations of 5 mg ramipril with 12.5 and 25 mg HCT and 10 mg ramipril with 12.5 mg HCT consistently produced significantly greater blood pressure reductions than their respective components. Response surface analyses were performed, and a stairstep model was constructed to characterize the shape of the dose-response surface. The combinations involving 5 and 10 mg ramipril with 12.5 and 25 mg HCT were again more effective than their components. Withdrawals and adverse effects were minimal for all treatments. A large drop in serum potassium was observed on 25 mg HCT, but not on combination therapy. Addition of ramipril appeared to reduce the hyperuricaemic effect of HCT. CONCLUSIONS: Several dosage combinations of ramipril plus HCT produced significantly greater blood pressure reductions than the monotherapies at the same dosages. Overall, the combination of 5 mg ramipril and 25 mg HCT gave the best mean reduction. Combination therapy with ramipril plus HCT was safe and effective for patients with mild-to-moderate essential hypertension.

Double-Blind Method↗
PubMed1993

Regulation of glycerol metabolism in Enterococcus faecalis by phosphoenolpyruvate-dependent phosphorylation of glycerol kinase catalyzed by enzyme I and HPr of the phosphotransferase system.

Using a polyclonal antibody against glycerol kinase from Enterococcus faecalis, we could demonstrate that glycerol kinase is inducible by growth on glycerol-containing medium and that during growth on glycerol the enzyme is mainly phosphorylated. Glucose and other sugars metabolized via the Embden-Meyerhof pathway strongly repressed the synthesis of glycerol kinase, while if glycerol was also present during growth, low activity, reflecting partial induction and the presence of mainly unphosphorylated, less active enzyme, was found. With gluconate, which is also a substrate of the phosphotransferase system, repression of glycerol kinase was less severe, but the enzyme was mainly present in the less active, unphosphorylated form. Effects of growth on different carbon sources on glycerol uptake are also reported.

Bacterial Proteins↗
PubMed1993

Effects of neurotensin and neuropeptide Y on coronary circulation and myocardial function in dogs.

This study analyzed the effects of the neuropeptides, neurotensin, and human and porcine analogue, neuropeptide Y, in anesthetized open-chest dogs. The left anterior descending coronary artery was cannulated and perfused at constant pressure via a blood reservoir. Flow to the coronary cannula was measured by an electromagnetic flowmeter, and regional segment lengths were measured by sonomicrometer crystals. Neurotensin injected into the coronary cannula resulted in a dose-dependent increase of coronary flow; neuropeptide Y resulted in a decrease of coronary flow. Because these changes in flow were not explained by systemic hemodynamic effects or alterations in regional myocardial function, they were considered to be coronary dilatation or constriction. Coronary dilatation by neurotensin was not prevented by alpha- or beta-adrenoceptor blockade but was completely abolished by indomethacin or by lowering coronary perfusion pressure to 35 mmHg when depressed systolic segment shortening indicated myocardial ischemia. Coronary constriction by neuropeptides Y persisted at coronary perfusion pressure of 35 mmHg and was only attenuated by indomethacin. We conclude that in contrast to systemic effects, coronary vasodilatation by neurotensin is mediated by a prostanoid product of cyclooxygenase. Preactivation of the prostaglandin system may explain why neurotensin lost its coronary dilator effect during myocardial ischemia. Neuropeptide Y may elicit coronary constriction in addition to mechanic reduction of coronary flow resembling severe coronary stenosis.

Animals↗
PubMed1993

Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion.

BACKGROUND: One or more brief episodes of coronary artery occlusion protect or "precondition" the myocardium perfused by that artery from a subsequent episode of sustained ischemia. We sought to determine whether ischemic preconditioning protects only those myocytes subjected to brief coronary occlusion or whether brief occlusions in one vascular bed also limit infarct size and/or attenuate contractile dysfunction in remote virgin myocardium subjected to subsequent sustained coronary occlusion. METHODS AND RESULTS: In the preliminary limb of the study, six anesthetized dogs underwent four episodes of 5-minute circumflex branch occlusion plus 5-minute reperfusion, followed by 1 hour of sustained left anterior descending coronary artery occlusion and 4.5 hours of reflow. Subendocardial blood flow during left anterior descending coronary artery occlusion (measured by injection of radiolabeled microspheres) was 0.07 +/- 0.03 mL.min-1 x g tissue-1, similar to the value of 0.07 +/- 0.02 mL.min-1 x g-1 observed in a group of eight concurrent control dogs. However, infarct size (assessed by triphenyltetrazolium staining) in the circumflex preconditioned group averaged 4 +/- 1% of the myocardium at risk, significantly less (p < 0.05) than the value of 13 +/- 4% observed in the concurrent controls. An additional 18 dogs were then randomized to undergo either four episodes of circumflex branch occlusion (n = 8) or no intervention (n = 10) before 1 hour of left anterior descending coronary artery occlusion and 4.5 hours of reflow. Subendocardial blood flow averaged 0.08 +/- 0.02 versus 0.08 +/- 0.03 mL.min-1 x g-1 in the control versus circumflex preconditioned groups, yet infarct size was significantly smaller in circumflex preconditioned dogs than in the controls (6 +/- 2% versus 16 +/- 5% of the risk region; p < 0.05). At 4.5 hours following reperfusion, segment shortening in the left anterior descending coronary artery bed (assessed by sonomicrometry) averaged -21 +/- 19% of baseline in control animals versus 13 +/- 12% of baseline in the preconditioned group (p = NS). Circumflex preconditioning did not, however, have an independent beneficial effect on contractile function: Regression analysis revealed that the trend toward improved function in circumflex preconditioned dogs reflected the smaller infarct sizes in this group. CONCLUSIONS: Brief episodes of ischemia in one vascular bed protect remote, virgin myocardium from subsequent sustained coronary artery occlusion in this canine model. These data imply that preconditioning may be mediated by factor(s) activated, produced, or transported throughout the heart during brief ischemia/reperfusion.

Animals↗
PubMed1993

Does preconditioning protect the coronary vasculature from subsequent ischemia/reperfusion injury?

BACKGROUND: "Preconditioning" with brief episodes of coronary artery occlusion reduces infarct size caused by subsequent sustained ischemia. However, the effects of preconditioning on the coronary vasculature are poorly understood. We sought to determine whether preconditioning would attenuate "low reflow" (ie, the deterioration in resting myocardial perfusion) and blunt the loss in coronary vasodilator reserve after sustained occlusion/reperfusion in the anesthetized open-chest canine model. METHODS AND RESULTS: Thirty-two dogs underwent 1 hour of sustained left anterior descending (LAD) coronary artery occlusion and 4 hours of reperfusion. Each dog was randomly assigned to the preconditioned group (four episodes of 5 minutes of LAD occlusion plus 5 minutes of reperfusion before sustained ischemia) or control group (no intervention). Submaximal vasodilator reserve was determined by measuring the increase in CBF in response to 0.01 mg acetylcholine (an endothelium-dependent dilator) and 0.05 mg nitroglycerin (an endothelium-independent dilator); low reflow was assessed by measurement of regional myocardial blood flow at 30 minutes and 4 hours after reflow; and infarct size was delineated by triphenyltetrazolium staining. In protocol 1 (n = 14), vasodilator reserve was measured at baseline and at 30 minutes and 4 hours after reflow. There was no change in the response to acetylcholine and nitroglycerin at 30 minutes after reperfusion compared with baseline. However, all dogs exhibited a loss in vasodilator reserve during the subsequent 3.5 hours of reflow, with no difference between control and preconditioned groups. That is, in control dogs, acetylcholine increased CBF from a baseline value of 10.1 +/- 1.3 mL/min to 18.0 +/- 2.6, 18.2 +/- 2.1, and 15.4 +/- 1.7 mL/min before occlusion, 30 minutes after reflow, and 4 hours after reperfusion, respectively (P < .05 for 30 minutes vs 4 hours after reperfusion). Similarly, in the preconditioned group, acetylcholine increased CFB from a baseline value of 12.0 +/- 2.9 mL/min to 19.6 +/- 3.8, 23.6 +/- 5.3, and 15.6 +/- 3.5 mL/min, respectively (P < .01 for 30 minutes vs 4 hours after reperfusion; P = NS between groups). In addition, all dogs exhibited low reflow, with no difference between control and preconditioned groups: subendocardial blood flow deteriorated between 30 minutes and 4 hours after reflow, from 0.91 +/- 0.20 to 0.40 +/- 0.03 mL min-1 x g-1 in control animals (P = .05 for 30 minutes vs 4 hours after reperfusion) and from 1.03 +/- 0.25 to 0.35 +/- 0.02 mL.min-1 x g-1 in the preconditioned group (P < .05 for 30 minutes vs 4 hours after reperfusion). However, all dogs in protocol 1 had small infarcts (3 +/- 1% and 2 +/- 1% of the risk region in control and preconditioned groups; P = NS), suggesting that control dogs may have been "preconditioned" by the vasodilators. An additional 18 dogs were entered into protocol 2, which was identical to protocol 1 except that acetylcholine and nitroglycerin were given only after reperfusion. In this case, we observed the expected reduction in infarct size in preconditioned dogs vs control dogs (2 +/- 1% vs 11 +/- 3% of the risk region; P < .01). However, the loss in vasodilator reserve was similar to that observed in protocol 1, with no difference between groups. Subendocardial blood flow at 30 minutes after reperfusion was higher in control animals than in preconditioned dogs (1.84 +/- 0.50 vs 0.74 +/- 0.08 mL.min-1 x g-1; P < .05), but subendocardial flow then deteriorated during the subsequent 3.5 hours to a similar value in both groups (0.55 +/- 0.11 and 0.50 +/- 0.06 mL.min-1 x g-1 in control and preconditioned dogs; P < .05 vs 30 minutes after reperfusion for both groups). CONCLUSIONS: The protective effects of preconditioning do not extend to the coronary vasculature in this canine model: Preconditioning neither prevented the deterioration in resting myocardial perfusion nor blunted the loss in submaximal vasodilator reserve obs

Acetylcholine↗
PubMed1993

p53 alterations in human squamous cell carcinomas and carcinoma cell lines.

p53 alterations were studied in a group of 22 primary squamous cell carcinomas (SCC) of the head and neck and in 10 cell lines derived from SCC. Positive immunohistochemical detection of p53 was accomplished in 10 of 22 primary tumors and in 7 of 10 SCC cell lines. Loss of heterozygosity of chromosome 17p, were the p53 gene is localized, was seen in five of seven SCC lines studied. DNA sequencing of the p53 gene of these five cell lines that had lost one allele showed p53 mutations in the remaining allele. In addition, from six primary SCC that exhibited loss of heterozygosity of chromosome 17p, three showed missense mutations of the p53 gene. The mutations of primary tumors and SCC cell lines were scattered in the midregion of the gene, affecting codons 151, 155, 174, 194, 220, 248, and 273. Five of these mutations modified guanine residues, a phenomenon that has been associated with the effect of carcinogens contained in tobacco smoke. Collectively these data show that approximately 50% of primary tumors and cell lines derived from SCC of the head and neck showed abnormalities of the p53 gene. In addition, it is of interest to note that the most invasive cell lines, as determined in an in vivo assay using xenotransplantation of tumor cells into denuded rat tracheal grafts, exhibited the most intense staining. Similarly, of five very advanced primary tumors, four showed intense p53 immunostain. These observations support the evidence that alterations in this tumor suppressor gene could be related to late events in tumor progression.

Carcinoma↗
PubMed1993

Pathogenesis and pathology of African trypanosomosis in Baoulé, N'Dama/Baoulé cross bred and Zebu cattle in Burkina Faso. 1. Clinical performance under high natural tsetse challenge.

The pathogenesis and pathology of African animal trypanosomosis (AAT) in Baoulé, N'Dama/Baoulé-cross-bred and Zebu cattle was studied from 1987 to 1991 in a series of experiments conducted under natural and artificial conditions of challenge at the Centre de Recherches sur les Trypanosomoses Animales (CRTA) in Burkina Faso. This first paper reports on the clinical performance of 64 Baoulé, 10 N'Dama/Baoulé-cross-bred and 20 Zebu cattle, which were transferred to the pastoral zone of Satiri, 50 km northeast of Bobo-Dioulasso, a zone infested with Glossina palpalis gambiensis, G. morsitans submorsitans and G. tachinoides. Prior to the experiment, the cattle had been raised in a fly proof stable and at the CRTA breeding station, an area of extremely low incidence of trypanosomosis or had been exposed at least once to natural trypanosome challenge in an area of high Glossina density. The cattle were monitored daily for clinical performance. Blood samples were collected twice weekly and examined on the spot for packed red cell volume (PCV) and parasitaemia. In the blood of 98% of the cattle trypanosomes (Trypanosoma vivax, T. congolense) were detected. Significant inter- and intrabreed differences with respect to the clinical performance were recorded. Regarding general health, the humpless Baoulé and N'Dama/Baoulé cross-bred cattle (Bos taurus) proved to be superior to the humped Zebu cattle (B. indicus) under this high challenge. Previous exposure to natural challenge had a positive effect on survival for both Baoulé and Zebu cattle. The phenotypic variation in response to trypanosomosis was small in Baoulé previously exposed and large in Baoulé previously not exposed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Development of multiple drug resistance of Trypanosoma congolense in Zebu cattle under high natural tsetse fly challenge in the pastoral zone of Samorogouan, Burkina Faso.

Preliminary data from an ongoing epidemiological survey in the pastoral zone of Samorogouan (Kénédougou) indicate the occurrence of multiple-drug-resistant Trypanosoma congolense. Despite frequent trypanocidal drug treatments with diminazene aceturate (Berenil, Hoechst) at 7 mg/kg body weight (bw) at intervals of 2 to 4 weeks, no significant drop in the prevalence of African animal trypanosomosis (AAT) was observed. To examine a suspected drug resistance, 20 Zebu cattle, naturally infected with T. congolense and/or T. vivax, were transferred in December 1989 from Samorogouan into a fly-proof stable. Diminazene aceturate at 7 mg/kg bw cured infections of T. vivax, but was ineffective against T. congolense. Likewise, treatments with homidium bromide (Ethidium, FBC) at 1 mg/kg bw and isometamidium chloride (Trypamidium, Rhône Mérieux) at 1 mg/kg bw, respectively, proved to be ineffective. Corresponding chemotherapeutic trials in previously unexposed Zebu bulls and Sahelian goats infected with one primary T. congolense isolate from Samorogouan demonstrated a high level of resistance to diminazene aceturate (7 mg/kg bw in cattle and 17.5 mg/kg bw in goats), isometamidium chloride (1 and 2 mg/kg bw i.v. in goats) and quinapyramine sulphate (Trypacide'S', Rhône Mérieux) at 5 mg/kg bw in goats. The appearance of a multiple-drug-resistant strain of T. congolense emphasizes the urgent need for new chemical substances as trypanocidal drugs and the increasing importance of efficient vector control.

Animals↗
PubMed1992

Reperfusion of hibernating myocardium: contractile function, high-energy phosphate content, and myocyte injury after 3 hours of sublethal ischemia and 3 hours of reperfusion in the canine model.

Hibernating myocardium has been defined as a persistent impairment of contractile function resulting from reduced coronary blood flow that can be partially or completely resolved once coronary perfusion is restored. In fact, recent clinical reports have documented a dramatic improvement in contractile function after relief of chronic sublethal ischemia. To investigate the phenomenon of sublethal ischemia followed by reperfusion, we assessed myocyte morphology, high-energy phosphate content, and regional contractile function in dogs undergoing (1) 3 hours of subtotal coronary artery occlusion (CO) and 3 hours of reflow or (2) 3 hours of total CO followed by reflow, in which myocyte viability was maintained by extensive collateral perfusion during ischemia (total CO/negligible necrosis). Data were compared with findings in a third group of dogs with total CO and low collateral blood flow during ischemia, in which large confluent infarcts developed. Endocardial blood flow averaged 30 +/- 6% (p less than 0.01) and 27 +/- 4% (p less than 0.01) of baseline preocclusion values during ischemia in the groups with subtotal CO and total CO/negligible necrosis, versus 3 +/- 1% of baseline values in dogs with total CO/confluent necrosis. Both the subtotal CO and total CO/negligible necrosis groups exhibited only mild-to-moderate reversible myocyte injury (assessed by electron microscopy) and had essentially no necrosis: infarct size was 1 +/- 1% (p less than 0.01) and 4 +/- 2% (p less than 0.01) of the risk region in the subtotal CO and total CO/negligible necrosis groups, versus 55 +/- 9% of the risk region in the total CO/confluent necrosis group. Furthermore, myocardial high-energy phosphate stores were in part preserved in all dogs that underwent sublethal ischemia: endocardial adenosine triphosphate (ATP) content was 55 +/- 11% (p less than 0.01) and 56 +/- 8% (p less than 0.01) versus 11 +/- 2% of baseline values in the subtotal CO, total CO/negligible necrosis, and total CO/confluent necrosis groups, respectively. At 3 hours post occlusion, segment shortening averaged +21 +/- 10% of baseline values in dogs with subtotal CO, (p less than 0.01 versus both total CO groups), -29 +/- 9% in dogs with total CO/negligible necrosis, and -36 +/- 13% in dogs with total CO/confluent necrosis. Reperfusion after sublethal ischemia produced an acute improvement in contractile function in both the subtotal CO and total CO/negligible necrosis groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1992

Structural and developmental analysis of two linked myosin heavy chain genes.

We have identified at the molecular level two murine myosin heavy chain (MHC) genes which encode adult skeletal isoforms. As is the case for the murine cardiac MHC genes, the genes are closely linked, head to tail. To identify the isoform encoded by each gene, we located and sequenced the 3' termini and assessed the genes' temporal and tissue-specific expression patterns using probes specific for the 3' untranslated regions. These analyses indicate that the myosin encoded by the gene located 5' in the linked pair is the murine 2A isoform. The isoform encoded by the 3'-most gene of the linked pair appears to encode an additional isoform that is expressed in a number of adult skeletal muscles. The pattern of expression of the 3'-most gene indicates that it is tightly controlled developmentally. Transcripts from this gene, when compared to those from the MHC2A and beta-MHC genes, are the predominant MHC transcripts found in the diaphragm, tongue, soleus, and masseter, indicating that it encodes a major skeletal MHC isoform.

Animals↗
PubMed1992

Determinants of coronary effects of atrial natriuretic factor in dogs.

The direct vascular action of atrial natriuretic factor (ANF) is unclear. In coronary vasculature, vasodilation has been reported as well as vasoconstriction. Doses of ANF, baseline plasma ANF levels and interference with the renin-angiotensin system might account for the controversy. We tried to further analyse determinants of the effect of ANF on coronary blood flow in anaesthetized dogs. The chest was opened and the left anterior descending coronary artery cannulated and perfused at constant normal (= 76 +/- 5 mmHg, n = 10) or reduced (= 37 +/- 3 mmHg, n = 10) pressure from the femoral arteries. At normal coronary perfusion pressure, ANF (1 ng kg-1 i.c.) reduced coronary flow from 30.7 +/- 4.2 to 26.9 +/- 4.0 ml min-1 (P less than 0.05). This effect was no longer significant at reduced coronary perfusion pressure (4.9 +/- 0.8 vs. 4.6 +/- 0.7 ml min-1). ANF (1 ng kg-1 i.c.) reduced coronary blood flow in correlation with baseline plasma ANF levels (r = 0.77, P less than 0.001). However the large variability of the constrictor effect of ANF in the rather small range of baseline plasma ANF, weakens the importance of this result and suggests other additional determinants. ANF (100 ng kg-1 i.c.) significantly increased coronary blood flow by 16-23% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Prevention with angiotensin-converting enzyme (ACE) inhibitors].

Preventive therapy by angiotensin-converting-enzyme (ACE) inhibitors is considered in hypertension and, more recently, in chronic heart failure. The mechanism of action of ACE-inhibitors is complex; most extensively studied, however, is their inhibitory effect on angiotensin-II production. ACE-inhibitors may act as vasodilators, reducing pre- and afterload. On the other hand, local renin-angiotensin systems may control growth processes both in myocardial and in smooth muscle cells. This may be another site of action for ACE-inhibitors. ACE-inhibitors are reliable antihypertensive drugs and may have additional specific effects on the heart and vascular smooth muscle. Clear evidence is, however, missing for their superiority above other drugs in preventing cardiovascular complications of hypertension. Most recently, the data of the "study of left-ventricular dysfunction" (SOLVD) and "survival and ventricular enlargement" (SAVE) study became available. These studies showed that ACE-inhibitors could prevent the incidence of heart failure in about one-third of patients with severe left-ventricular dysfunction during 3 years of observation when compared with placebo treated patients. A new indication, therefore, for ACE-inhibitors could be left ventricular dysfunction after myocardial infarction. It remains unclear 1) what could be the adequate diagnostic procedures to identify patients for preventive treatment, 2) when therapy should be started, 3) about the duration of therapy, 4) about the doses of ACE-inhibitors for this indication, 5) what will be the side-effects when used in a broader population, and 6) will this prevention of heart failure be a specific effect of ACE-inhibitors?

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

The residual effect of deltamethrin Spot On when tested against Glossina palpalis gambiensis under fly chamber conditions.

Groups of single zebu cattle were exposed to infestations of the tsetse fly Glossina palpalis gambiensis in fly chambers following treatment with a pour on formulation of deltamethrin, Coopers* Spot On. During the experiment one animal was maintained in a stall, the other exposed at intervals to sunlight. Both mortality and knockdown of exposed flies was demonstrated. Mortality rates of greater than 90% were recorded during the period 0-20 days after treatment and values in excess of 50% during the period, 41-59 days after treatment. Knockdown was more marked with rates in excess of 90% and 65% being recorded for respectively 45 and 75 days after treatment. Exposure to sunlight did not significantly effect the performance of Spot On. Flies were observed to repeatedly land on the deltamethrin treated cattle, so contributing to the overall pick-up of effective concentrations of the chemical. It was considered that this effect of the chemical could considerably reduce the risk of transmission of trypanosomosis from the start of a tsetse campaign.

Administration, Topical↗
PubMed1992

Simultaneous control of ticks and tsetse flies in Satiri, Burkina Faso, by the use of flumethrin pour on for cattle.

Treatments of 2000 cattle at monthly intervals with flumethrin pour on (1 mg active ingredient/kg b.w.) resulted in a rapid decrease of African Animal Trypanosomosis (AAT). After an initial curative treatment of the sentinel herd with diminazene aceturate (7 mg/kg b.w.) only positive cases were treated. Three applications of flumethrin were sufficient to reduce the prevalence of AAT to below 5%. Apart from a slight increase at the end of the first year the infection rate varied between 0 and 5%. A tsetse population disappeared from a heavily infested habitat after six treatments. The average tick infestation was 3-10 times lower than in a control site inspite of the repeated use of another acaricide. Between 3282 and 8624 animals were treated five times in the second year at intervals of about two months. 130 monoconical insecticide impregnated traps were deployed in habitats which were inaccessible for the cattle. The highest infection rate of the sentinel herd was 1.4%. Among another 150 eartagged cattle scattered over a district of about 1000 m2 the prevalence of AAT dropped to 4.8% at the end of the second year. Emphasis is put on an active and financial participation of the rural communities to ensure a viable campaign and good prospects of a taking over by local organizations once the external interventions have stopped.

Administration, Topical↗
PubMed1991

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

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

Animals↗
PubMed1991

Effect of mediators on coronary circulation.

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

Adrenal Glands↗