Biomedical subjects

R J Diaz

Publications and source records attributed to R J Diaz.

At least 19 recordsLinked to original sources

PubMed2006

The challenge of diagnosing atopic diseases: outcomes in Cuban children depend on definition and methodology.

BACKGROUND: Prevalences of childhood asthma and other atopic diseases are increasing worldwide, and so is the number of diagnostic methods and definitions used. We determined the occurrence of atopic diseases in Cuban children with a range of diagnostic approaches commonly used or proposed in epidemiological studies, and compared the different outcome measures. METHODS: A total of 398 Cuban schoolchildren between 5 and 13 years of age were diagnosed by International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, clinical examination, pre- and post-exercise spirometry, and skin prick testing. All results were considered separately, as well as jointly by using scores and definitions as described in the literature. RESULTS: Using questionnaire-based approaches, 21-39% of the children were positive for asthma, 9-19% for atopic dermatitis, and 15-46% for rhinoconjunctivitis. With spirometry, 7% of the children had asthma. Definitions based on a combination of questionnaire and spirometry results yielded asthma rates of 5%. Of all children, 6% wheezed on clinical examination, and only one child showed clinical signs of atopic dermatitis. Eleven percent of the children had a positive skin prick test. In total, 254 children (64%) had an atopic disease as based on the ISAAC questionnaire, and 263 (66%) based on all approaches used. CONCLUSION: Diagnostic outcomes on atopic diseases vary considerably depending on definition and methodology. Our results clearly demonstrate the need for consensus on diagnosing asthma and other atopic diseases in epidemiological studies. Based on the most commonly used ISAAC questionnaire, our data suggest prevalences of atopic diseases in Cuban children that rival those found in some other Latin American countries and developed nations with the highest prevalences in the world.

Adolescent↗

PubMed2001

Chloride channel inhibition does block the protection of ischemic preconditioning in myocardium.

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Angiogenesis Inhibitors↗

PubMed1999

Chloride channel inhibition blocks the protection of ischemic preconditioning and hypo-osmotic stress in rabbit ventricular myocardium.

The objective of this study was to examine the role of chloride (Cl-) channels in the myocardial protection of ischemic preconditioning (IP). Isolated rabbit ventricular myocytes were preconditioned with 10-minute simulated ischemia (SI) and 20-minute simulated reperfusion (SR) or not preconditioned (control). The myocytes then received 180-minute SI or 45-minute SI/120-minute SR. Indanyloxyacetic acid 94 (IAA-94, 10 micromol/L) or 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB, 1 micromol/L) was administered before IP or before SI or SI/SR to inhibit Cl- channels. Electrophysiological studies indicate that these drugs, at the concentrations used, selectively abolished Cl- currents activated under hypo-osmotic conditions (215 versus 290 mOsm). IP significantly (P<0.001) reduced the percentage of dead myocytes after 60-minute (30.8+/-1.3%, mean+/-SEM), 90-minute (35.3+/-1.3%), and 120-minute (39.2+/-1.7%) SI compared with controls (44.7+/-1.6%, 54.5+/-1.3%, and 58.9+/-1.8%, respectively) and after 45-minute SI/120-minute SR (36.3+/-0.6%) compared with control (56.6+/-2.2%). Hypo-osmotic stress also produced protection similar to IP. IAA-94 or NPPB abolished the protection of both IP and hypo-osmotic stress. In buffer-perfused rabbit hearts preconditioned with three 5-minute ischemia/10-minute reperfusion cycles given before the 40-minute long ischemia and 60-minute reperfusion, IP significantly (P<0.0001) reduced infarct size (IP+vehicle, 4.7+/-0.9%, versus control+vehicle, 26.6+/-3.3%; mean+/-SEM). Again, IAA-94 or NPPB abolished the protection of IP. Our results implicate Cl- channels in the IP protection of the myocardium against ischemic/reperfusion injury and demonstrate that hypo-osmotic stress is capable of preconditioning cardiomyocytes.

Alkaloids↗

PubMed1998

Preferential regulation of rabbit cardiac L-type Ca2+ current by glycolytic derived ATP via a direct allosteric pathway.

1. The activity of Ca2+ channels is regulated by a number of mechanisms including direct allosteric modulation by intracellular ATP. Since ATP derived from glycolysis is preferentially used for membrane function, we hypothesized that glycolytic ATP also preferentially regulates cardiac L-type Ca2+ channels. 2. To test this hypothesis, peak L-type Ca2+ currents (ICa) were measured in voltage-clamped rabbit cardiomyocytes during glycolytic inhibition (2-deoxyglucose + pyruvate), oxidative inhibition (cyanide + glucose) or both (full metabolic inhibition; FMI). 3. A 10 min period of FMI resulted in a 40.0 % decrease in peak ICa at +10 mV (-5.1 +/- 0.6 versus -3.1 +/- 0.4 pA pF-1; n = 5, P < 0.01). Similar decreases in peak ICa were observed during glycolytic inhibition using 2-deoxyglucose (-6.2 +/- 0.2 versus -3.7 +/- 0.2 pA pF-1; n = 5, P < 0.01) or iodoacetamide (-6.7 +/- 0.3 versus -3.7 +/- 0.2 pA pF-1; n = 7, P < 0.01), but not following oxidative inhibition (-6.2 +/- 0.4 versus -6.4 +/- 0.3 pA pF-1; n = 5, n.s.). The reduction in ICa following glycolytic inhibition was not mediated by phosphate sequestration by 2-deoxyglucose or changes in intracellular pH. 4. Reductions in ICa were still observed when inorganic phosphate and creatine were included in the pipette, confirming a critical role for glycolysis in ICa regulation. 5. With 5 mM MgATP in the pipette during FMI, peak ICa decreased by only 18.4 % (-6.8 +/- 0.6 versus -5.5 +/- 0.3 pA pF-1; n = 4, P < 0.05), while inclusion of 5 mM MgAMP-PCP (beta,gamma-methyleneadenosine 5'-triphosphate, Mg2+ salt) completely prevented the decrease in peak ICa (-6.9 +/- 0.3 versus -6.5 +/- 0.3 pA pF-1; n = 5, n.s.). 6. Together, these results suggest that ICa is regulated by intracellular ATP derived from glycolysis and does not require hydrolysis of ATP. This regulation is expected to be energy conserving during periods of metabolic stress and myocardial ischaemia.

Adenosine Triphosphate↗

PubMed1997

Ischemic preconditioning: differences in protection and susceptibility to blockade with single-cycle versus multicycle transient ischemia.

BACKGROUND: We compared ischemic preconditioning (IP) induced with a single cycle of transient ischemia and reperfusion with that induced by multiple cycles in terms of (1) efficacy of protection against myocardial necrosis and (2) susceptibility to pharmacological blockade by inhibition of protein kinase C (PKC) or elevation of cAMP. METHODS AND RESULTS: All rabbits were subjected to 30 minutes of regional ischemia and 90 minutes of reperfusion in vivo. IP was induced with either one or three cycles of 5-minute transient ischemia and 10-minute reperfusion given before the 30-minute ischemia. Drug-treated hearts received a bolus dose of one of the following just before the 30-minute ischemia: (1) the PKC inhibitor chelerythrine (3.8 mg/kg), (2) the PKC inhibitor polymyxin B (10 mg/kg), or (3) the cAMP-increasing agent NKH477 (45 microg/kg). IP induced with either one or three cycles of transient ischemia and reperfusion significantly protected the heart against infarction, although the extent of protection was significantly greater with three-cycle IP. Chelerythrine, polymyxin B, or NKH477 alone did not alter infarct size in control hearts, nor did they increase infarct size in hearts preconditioned with three-cycle IP. In contrast, when IP was induced with only a single cycle, all three of these drugs significantly increased infarct size above that of the untreated one-cycle IP group. However, infarct size in all three of these drug-treated one-cycle IP groups was still significantly lower than that in the corresponding drug-treated controls, indicating a partial block of IP. CONCLUSIONS: Three-cycle IP provided more effective protection against myocardial necrosis than one-cycle IP and was less susceptible to blockade by inhibitors of PKC or an agent that increases cAMP levels. However, single-cycle IP was only partially blocked by either inhibition of PKC or stimulation of cAMP production. Neither activation of the PKC pathway nor reduced formation of cAMP alone fully accounted for the necrosis protection by IP even when induced with only a single cycle of transient ischemia.

Adenylyl Cyclases↗

PubMed1997

Selective blockade of AT1 angiotensin II receptors abolishes ischemic preconditioning in isolated rabbit hearts.

The aim of the present study was to assess the participation of angiotensin II receptors in the triggering mechanism of ischemic preconditioning. Isolated buffer-perfused rabbit hearts were subjected to 40 min of regional ischemia (37 degrees C) followed by 60 min of reperfusion. Ischemic preconditioning was induced with three cycles of 5-min ischemia and 10-min reperfusion given prior to the 40-min ischemic period. Infarct size and ventricular function were assessed. Ischemic preconditioning reduced infarct size to 5.2 +/- 1.2% of the area at risk (mean +/- S.E.M., P<0.001) when compared to controls (26.4 +/- 3.0%), but did not protect against ventricular dysfunction. Activation of angiotensin II receptors with angiotensin II (100 nM) also limited infarct size (9.6 +/- 2.2%, P<O.01 v control group). Inhibition of angiotensin II receptors with [Sar1, Val5, Ala8]-angiotensin II (saralasin, 1 microM) blocked the protection of ischemic preconditioning against necrosis (29.7 +/- 3.2%) while it did not increase infarct size in saralasin-treated control hearts (31.5 +/- 3.9%). Furthermore, inhibition of the AT1 subtype of the angiotensin II receptor with losartan (20 microM), but not inhibition of the AT2 subtype with PD-123,319 ditrifluoroacetate (10 microM), abolished the infarct size-limiting effect of ischemic preconditioning. We conclude that the AT1 angiotensin II receptor participates in ischemic preconditioning. Thus, in the isolated rabbit heart, activation of AT1 receptors must occur before prolonged ischemia for ischemic preconditioning to limit infarction.

Analysis of Variance↗

PubMed1996

Graded effect of tailless on posterior gut development: molecular basis of an allelic series of a nuclear receptor gene.

By marking cells of early gastrula stage embryos, we showed that in embryos mutant for a strong tll allele the fate map is shifted posteriorly and the hindgut anlage is deleted. We therefore used aspects of hindgut development to characterize the phenotype of new and previously described tll alleles. In embryos mutant for the various alleles, relative levels of blastoderm expression of Trg (T-related gene, required to establish the hindgut) and of mature hindgut size were determined; the results of these assays correlated with each other. Of the alleles that map to the sequence encoding the Tailless nuclear receptor protein, all (four) affect the zinc fingers of the DNA binding domain; surprisingly, substitutions of highly conserved residues allow a range of activities as detected by our bioassays.

Alleles↗

PubMed1996

Effect of ischemic preconditioning of the myocardium on cAMP.

Reduction of cAMP has been implicated in the protection of ischemic preconditioning (IP), but until now, this possibility has not been directly addressed. In this study, we found that in the in vivo rabbit heart 10 to 30 minutes of sustained regional ischemia was accompanied by a nearly twofold rise in cAMP levels. This increase in cAMP was attenuated when sustained ischemia was preceded by IP induced with a single cycle of transient ischemia and reperfusion (TI/R) and prevented when ischemia was preceded by three cycles of TI/R. The mechanism of cAMP reduction by IP does not involve activation of protein kinase C (PKC), since the PKC inhibitor polymyxin B (24 mg/kg) did not raise cAMP levels during sustained ischemia in IP hearts. Furthermore, this effect is also not mediated by reduced responsiveness of the beta-adrenergic effector pathway, since both nonischemic hearts and hearts subjected to three cycles of TI/R exhibited similar increases in cAMP in response to 5 micrograms/kg isoproterenol. However, propranolol (0.75 mg/kg) abolished the rise in cAMP levels observed during sustained ischemia in control hearts but did not reduce cAMP levels further in IP hearts. These data indicate that the ischemia-induced rise in cAMP levels in control hearts was mediated by activation of the beta-adrenergic receptor. Taken together with data demonstrating that beta-adrenergic responsiveness was not affected by IP, these data support the conclusion that the lack of elevation in cAMP levels observed during sustained ischemia in IP hearts is mediated by an attenuation of norepinephrine release. To examine whether the protection of IP against necrosis was mediated by the lack of elevation in cAmp levels, we determined whether the infarct size-limiting effect of IP could be blocked by NKH477, an activator of adenylyl cyclase. Four groups or rabbits were subjected to 30 minutes of in vivo regional ischemia and 90 minutes of reperfusion. Control hearts (n = 10) had 53.6 +/- 5.5% infarction of the area at risk. IP with three cycles of transient ischemia limited infarct size to 3.2 +/- 1.3% (N = 13, p < .0001). NKH477 (45 micrograms/kg) increased average cAMP levels in IP hearts during sustained ischemia to levels similar to those in untreated control hearts. However, NKH477 did not block IP (50.2 +/- 7.7% of the area at risk was infarcted in the control +NKH477 group [n = 10] versus 10.0 +/- 5.9% in the IP + NKH477 group [n = 7], P < .05). Therefore, we conclude that although IP lowers cAMP levels during sustained ischemia, this effect is not necessary for its protection against necrosis, since raising cAMP does not block this protection of IP.

Adenylyl Cyclases↗

PubMed1994

Evidence that increases in lymphocyte tyrosine phosphorylation precede cardiac allograft rejection. Effects of cyclosporine and potential use in clinical management.

Tyrosine phosphorylation is an early, critical event in lymphocyte signal transduction. We measured tyrosine phosphorylation in a porcine experimental transplant model to evaluate its utility in monitoring the allograft immune response. Using flow cytometry, we demonstrate a biphasic increase in phosphotyrosine (ptyr) levels in peripheral blood mononuclear cells (PBMC), and that increases are detectable as early as 1 day posttransplantation in untreated transplanted animals (n = 4). This biphasic response is likely result from the sequestration of ptyr+ cells from the periphery into the graft as graft-infiltrating lymphocytic cells show increased ptyr levels. This suggests possible lymphocyte trafficking between the peripheral compartment and the allograft. A 5-day course of treatment with cyclosporine (CsA) at 20 mg/kg/day (n = 4), but not at 10 mg/kg/day (n = 4), prevents graft rejection in this allograft model. Strikingly, treatment with 20 mg/kg/day CsA, but not with 10 mg/kg/day, suppressed increases in ptyr levels in both PBMC and graft-infiltrating cells. Increases in ptyr levels in PBMC are detectable 2-5 days before histologic and electrocardiographic signs of graft rejection, suggesting a potential diagnostic utility for measuring tyrosine phosphorylation in monitoring and managing transplant rejection.

Animals↗

PubMed1993

The effect of dialyzer reprocessing on performance and beta 2-microglobulin removal using polysulfone membranes.

Increased biocompatibility and lower cost are the two major arguments favoring routine dialyzer reprocessing. The impact of longer-term reprocessing is critical to the practical use of polysulfone membranes (PMs), because of the possibility of decreasing efficiency and performance, especially in the removal of beta 2-microglobulin (beta 2M), a protein that has been implicated in the development of dialysis-associated amyloidosis (DDA). In this study, we examine urea clearance (Kd), urea mass transfer coefficient (h0), ultrafiltration coefficient (K(uf)), and percent removal of beta 2M up to 24 uses. The study involved 11 patients on hemodialysis for 5.27 +/- 4.6 years, with a mean age of 62.5 +/- 9.7 years and average run-time treatment of 2.78 +/- 0.3 hours. PMs were tested after being reprocessed manually using bleach and formaldehyde. The efficacy of the dialyzer was examined on uses 1, 5, 10, 15, 20, and 24, and the percent removal of beta 2M was determined except in the twentieth use and corrected for ultrafiltration. The Kd obtained through 24 uses showed no significant change, although h0 was significantly increased in the fifteenth use, and K(uf) was significantly increased in the 10th and 20th use (P < 0.05). The percent removal of beta 2M increased significantly from 44.1 +/- 2.8 (mean +/- SEM) in the first use to 59.4 +/- 2.19 (P < 0.05) in the 10th use, and 62.1 +/- 4.07 and 63.1 +/- 4.27 in the 15th and 24th uses, respectively (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Comparison of ischaemic preconditioning in blood perfused and buffer perfused isolated heart models.

OBJECTIVE: The aim was to compare the effects of ischaemic preconditioning in the buffer perfused and parabiotic blood perfused Langendorff rabbit heart models. METHODS: Isolated hearts were perfused with either Krebs-Henseleit buffer solution or blood from a support rabbit. Hearts were subjected to an initial 30 min stabilisation period followed by 30 min of global ischaemia and 60 min of reperfusion. Ischaemic preconditioned (IP) hearts were also subjected to one cycle of 5 min global ischaemia and 10 min of reperfusion before the 30 min ischaemia. For each experiment, left ventricular function and necrosis were measured. RESULTS: Necrosis, as measured by tetrazolium staining and expressed as a percentage of the left ventricular area, was significantly different between the buffer perfused control [42.5% (SEM 6.9), n = 7] and buffer perfused IP group [22.2% (5.4), n = 7, p < 0.01]. In the blood perfused experiments, the IP group also had less necrosis [9.3% (3.1), n = 9] as compared to controls [22.9%(4.2), n = 9, p < 0.01]. The percentage reduction in necrosis produced by ischaemic preconditioning was not significantly different between the buffer perfused and blood perfused models. Peak left ventricular systolic pressure was not different between the control and IP hearts in either model at any time during the 60 min reperfusion period. In buffer perfused hearts, left ventricular end diastolic pressure at 60 min reperfusion was not significantly different between the IP and the control groups, at 34.3(5.5) mm Hg v 37.8(4.9) mm Hg, respectively. Similarly, there was no statistically significant difference in left ventricular end diastolic pressure in the blood perfused groups at this time: 13.3(2.8) in the IP group v 24.0(6.5) in controls. CONCLUSIONS: In isolated heart models of global ischaemia and reperfusion, in which both recovery of function and necrosis were assessed together, ischaemic preconditioning was highly effective in reducing necrosis in both blood perfused and buffer perfused models. However, ischaemic preconditioning did not significantly improve postischaemic recovery of function in either of the two preparations.

Animals↗

PubMed1993

The protective effect of magnesium on acute catecholamine cardiotoxicity in the neonate.

Neonates undergoing heart surgery are exposed to high levels of circulating catecholamines. Our objective was to determine to what extent administration of magnesium counters epinephrine-induced cardiotoxicity. We assessed left ventricular function (pressure-volume data obtained by the conductance catheter/micromanometer technique) and ultrastructure in newborn pigs 3 to 5 days of age before and after administration of epinephrine alone (2 micrograms/kg/min, group A, n = 6) and simultaneously with magnesium sulfate (8 mmol/L, 5 ml/hr, group B, n = 6). Plasma levels of magnesium were maintained at 200% to 250% of control, and ionized calcium was maintained at normal levels. During administration of epinephrine, there was a significant increase in end-systolic elastance from 8.9 +/- 2 to 15 +/- 3 mm Hg/ml in group A and from 7.8 +/- 2 to 16 +/- 3 mm Hg/ml in group B (p < 0.05). This increase was accompanied by an increase in chamber stiffness index (p < 0.05) and shortening of the time constant of isovolumic relaxation (p < 0.05; group A, 19 +/- 3 to 13 +/- 3 msec; Group B, 20 +/- 2 to 15 +/- 2 msec). After epinephrine was discontinued, however, systolic and diastolic indexes returned to baseline levels in group B, whereas group A exhibited a significant reduction in end-systolic elastance (5 +/- 1 mm Hg/ml; p < 0.05) and an increase in chamber stiffness index (0.7 +/- 0.08 versus 0.4 +/- 0.1 ml-1; p < 0.05) and time constant (25 +/- 1 versus 19 +/- 3 msec). Left ventricular dysfunction in group A was associated with focal sarcolemmal rupture and mitochondrial swelling, whereas only minor reversible changes (microvesicular lipid accumulation) were seen in group B. We conclude that magnesium has a protective effect against epinephrine-induced cardiotoxicity because of its blocking action on calcium influx of ionized calcium and could be of therapeutic benefit in the perioperative period.

Adenosine Triphosphate↗

PubMed1992

Behaviour modification in obese subjects with type 2 diabetes mellitus.

We have followed prospectively, 46 obese, type 2 diabetic patients for a 55-week period, in order to evaluate the efficiency of an educational programme based on behaviour modification to enhance weight loss and changes of other cardiovascular risk factors. No patient received pharmacological treatment during the study. At the end of the follow-up the patients obtained an average weight loss of 9.250 kg (range: 0.500-17.500 kg); the BMI was reduced from 34.2 +/- 0.8 kg/m2 to 30.6 +/- 1.1 kg/m2 (P less than 0.01); fasting serum glucose descended from 7.9 +/- 0.4 to 6.1 +/- 0.5 mM (P less than 0.05); SBP (systolic blood pressure) decreased from 145.7 +/- 3 to 126.4 +/- 5.1 mmHg (P less than 0.01); DBP (diastolic blood pressure) decreased from 83.5 +/- 2.5 to 65 +/- 2.6 mmHg (P less than 0.01); triglyceride levels were lowered from 164.5 +/- 12 to 109.7 +/- 10 mg/dl (P less than 0.01); HDL-cholesterol levels increased from 1.27 +/- 0.05 to 1.53 +/- 0.12 mM (P less than 0.01). Serum glucose 2 h after a 75 g glucose oral load decreased from 14.9 +/- 0.6 to 12.7 +/- 0.9 mM (P less than 0.05) on week 35 of follow-up. Twelve patients no longer presented a diabetic curve (8 normal oral glucose tolerance test (OGTT) curves, and 4 impaired glucose tolerance (IGT) curves). No significant changes in the parameters studied were obtained in the group of patients on conventional treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Behavior Therapy↗

PubMed1992

Pharmacodynamics and pharmacokinetics of cyclosporin A in the newborn pig.

The disposition kinetics of cyclosporin A in the neonates as well as age-related differences in lymphocyte responses to cyclosporin A are unknown. A single intravenous infusion of cyclosporin A was given to neonatal (2.5 or 5 mg/kg) and mature pigs (10 mg/kg) and blood cyclosporin A levels were measured by RIA. The neonates had longer elimination half-life and lower drug clearance than mature animals. Suppression in lymphocyte proliferation was only observed in mixed lymphocyte reaction and phytohemagglutinin-stimulated cultures of the 2-hour samples from neonates receiving 5 mg/kg. We conclude that neonatal pig exhibit different cyclosporin A pharmacokinetics and show higher sensitivity to cyclosporin A than mature animals.

Aging↗

PubMed1991

Age-related differences in the effects of cyclosporine on lymphocyte intracellular free calcium.

The effect of cyclosporine on lymphocyte intracellular free calcium [( Ca2+]i) is controversial, and potential age-related differences in lymphocyte CsA sensitivity have not been studied. We measured the mitogen-induced change in [Ca2+]i in peripheral blood lymphocytes (PBLs) following intravenous CsA infusion (5 mg/kg) in neonatal pigs and found a significantly reduced calcium response compared with control (P = 0.02). This was associated with an elevation in resting [Ca2+]i in the neonatal PBLs 24 hr following the CsA infusion (P = 0.02). These changes in lymphocyte [Ca2+]i were associated with suppression of cell proliferation. Neonatal PBLs in mixed lymphocyte cultures showed a greater PHA-induced change in [Ca2+]i (delta[Ca2+]i) compared with mature PBLs (P = 0.0007). The addition of CsA (1 microgram/ml) to mitogenic- and allogeneic-stimulated cultures did not affect resting [Ca2+]i or delta[Ca2+]i in either neonatal or mature PBLs. Our results demonstrate significant differences in calcium responses in neonatal lymphocytes following CsA infusion and allogeneic stimulation. This implies that there are age-related differences in CsA effects at or proximal to the level of calcium release and/or sequestration in the lymphocyte signal transduction pathway, and that elevated resting intracellular calcium levels may be indicative of reduced responsiveness, possibly through feedback inhibition of tyrosine kinase activity.

Aging↗

PubMed1991

Effect of rapid cooling contracture on ischemic tolerance in immature myocardium.

Hypothermic perfusion before cardioplegic ischemic arrest is commonly used in neonatal cardiac surgery. However, perfusion cooling of the heart in the nonarrested state results in an inotropic response and may induce myocardial contracture secondary to a sustained elevation of intracellular calcium levels. The effect of prearrest cardiac cooling was examined in two groups of isolated parabiotic, blood-perfused neonatal rabbit hearts. Group C (cooling group, n = 12) was exposed to 15 minutes of cold perfusion to 12 degrees C before 1 hour of cardioplegic arrest. Group N (normothermia group, n = 11) underwent identical arrest conditions but without prearrest cold perfusion. Developed pressure at constant volume in group C fell from 109 +/- 8.7 mm Hg at baseline to 55.2 +/- 5.5 mm Hg after 30 minutes of reperfusion versus no significant change in group N. Diastolic compliance showed significant deterioration in group C, with marked elevation of diastolic pressure from 9.8 +/- 0.4 mm Hg at baseline to 22.0 +/- 4.4 mm Hg after ischemia and reperfusion. This experimental data demonstrates that profound hypothermic perfusion of the myocardium in the nonarrested state may induce a rise in resting myocardial tension and that cardioplegic ischemic arrest in the presence of cooling contracture may result in important myocardial injury.

Animals↗

PubMed1991

Age-related response to epinephrine-induced myocardial stress. A functional and ultrastructural study.

Left ventricular systolic and diastolic function before, during, and after a 2-hour intravenous infusion of epinephrine at either 0.5 micrograms/kg/min or 2 micrograms/kg/min were assessed by pressure-volume data obtained by conductance catheter micromanometer technique and correlated with cardiac ultrastructure and plasma levels of epinephrine in neonatal (3-5 days old, n = 12) versus adult (3-4 months old, n = 11) pigs. Administration of epinephrine at 0.5 micrograms/kg/min resulted in an increase in end-systolic elastance (Ees) only in adults, whereas at 2.0 micrograms/kg/min Ees increased in both groups. After 2-hour administration of epinephrine at 2.0 micrograms/kg/min, Ees decreased significantly (p less than 0.05) from the preinfusion baseline value of 8.9 +/- 2 (mean +/- SD) to 5 +/- 1.7 mm Hg/ml, and a significant (p less than 0.05) increase in left ventricular volume elasticity (VdP/dV) from 0.4 +/- 0.02 to 1.4 +/- 0.2 mm Hg occurred in neonates versus no change from baseline in either Ees or VdP/dV in the adults. These changes in the neonates were associated with sarcolemmal rupture and mitochondrial Ca2+ granule deposition versus normal cardiac ultrastructure in the adults. We conclude that the neonatal myocardium is more susceptible to cardiotoxicity from circulating epinephrine.

Aging↗

PubMed1990

The Drosophila gene tailless is expressed at the embryonic termini and is a member of the steroid receptor superfamily.

The zygotically active tailless (tll) gene plays a key role in the establishment of nonmetameric domains at the anterior and posterior poles of the Drosophila embryo. We have cloned the tll gene and show that it encodes a protein with striking similarity to steroid hormone receptors in both the DNA binding "finger" and ligand binding domains. tll RNA is initially expressed in embryos in two mirror-image symmetrical domains; this pattern then quickly resolves into a pattern consistent with the mutant phenotype: a posterior cap and an anterior dorsal stripe. That the tll gene may also play a role in the nervous system is suggested by its strong expression in the forming brain and transient expression in the peripheral nervous system.

Amino Acid Sequence↗