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Biomedical subjects

R G Johnson

Publications and source records attributed to R G Johnson.

At least 91 records · Page 5Linked to original sources
PubMed1995

CABG after successful PTCA: a case-control study.

We sought characteristics predictive of the need for operative revascularization subsequent to a successful coronary angioplasty. Through June 1993, 128 patients who had successful percutaneous transluminal coronary angioplasty (PTCA) between January 1982 and March 1989 required subsequent coronary artery bypass grafting (CABG) at our hospital. These cases were matched with 128 controls who had a successful PTCA but did not require subsequent CABG. Controls were matched to cases by the date of their initial PTCA. Before initial PTCA there were no differences between the cases and controls in terms of age, sex, prior myocardial infarction, ejection fraction, duration of anginal symptoms, hypertension, hyperlipidemia, family history, or obesity (all not significant). A greater number of cases had diabetes (35 versus 18; p = 0.009). Angiography before initial PTCA revealed that cases had a greater mean number of total lesions (4.1 versus 3.3; p = 0.002) and a higher incidence of left anterior descending and circumflex artery stenoses of 70% or greater (98 versus 75 and 57 versus 34, respectively; p = 0.006). The mean number of lesions successfully dilated was greater in cases (2.4 versus 1.7; p = 0.0001). Cases had CABG at a mean interval of 16.7 +/- 23 months. There were 17 late deaths among cases and 9 among the controls at a mean of 38.6 +/- 30 months. The survival probability at 5 years was 94.5% for controls and 87.9% for cases (p = 0.048). Initial revascularization by PTCA is followed by CABG at a brief interval in a subset of patients who have markers of more severe disease than do patients who do not require early CABG.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1995

Adenosine triphosphate-sensitive K+ channels mediate postcardioplegia coronary hyperemia.

The purpose of the present study was to examine the role of adenosine triphosphate-sensitive potassium channels in mediating the coronary hyperemic response after crystalloid cardioplegia. Thirteen pigs were placed on normothermic cardiopulmonary bypass support. Hearts were arrested with cold (4 degrees C) crystalloid ([K+] 25 mmol/L) cardioplegic solution for 60 minutes. In seven of these pigs, hearts were then reperfused for 60 minutes with warm blood, and the animal was separated from cardiopulmonary bypass. The in vivo responses to the intracoronary administration of the K+ adenosine triphosphate channel blocker glibenclamide (50 gm/kg per minute) or the K+ adenosine triphosphate channel opener pinacidil (2 gm/kg per minute) were evaluated before cardiopulmonary bypass (baseline) and after 2 minutes and 60 minutes of reperfusion in the cardioplegia-reperfusion group. Under baseline conditions, glibenclamide and pinacidil induced a respective decrease and increase in coronary blood flow and an increase and a decrease in coronary vascular resistance. Coronary responses to glibenclamide and pinacidil were markedly enhanced after 2 minutes or 60 minutes of postcardioplegia reperfusion. In vitro responses of coronary arterioles (90 to 180 microns) were examined in a pressurized, no-flow state with video microscopy. The contractile response of coronary arterioles to glibenclamide and the relaxation response to pinacidil were significantly enhanced 2 minutes or 60 minutes after reperfusion (all p < 0.05 versus control). The response to pinacidil was markedly inhibited by glibenclamide, which confirms these antagonistic effects on K+ adenosine triphosphate channels. Decreased tissue concentrations of adenosine triphosphate in the coronary arterial smooth muscle and myocardium were observed after cardioplegia and persisted for up to 60 minutes of reperfusion (both p < 0.05 versus control). These results suggest that coronary hyperemia associated with postischemic cardioplegia is mediated in part by activation of K+ adenosine triphosphate channels in the coronary microcirculation.

Adenosine Triphosphate↗
PubMed1995

Discovery of L-162,313: a nonpeptide that mimics the biological actions of angiotensin II.

L-162,313 (5,7-dimethyl-2-ethyl-3-[[4-[2(n- butyloxycarbonylsulfonamido)-5-isobutyl-3-thienyl]phenyl]methyl]- imadazo[4,5-b]pyridine) is a nonpeptide that mimics the biological actions of angiotensin II (ANG II). The intravenous administration of L-162,313 increased blood pressure in the rat. The maximum increase in mean arterial pressure (MAP) was not different from the maximum response to ANG II in the same preparation. However, the duration of the pressor response after L-162,313 greatly exceeded that of ANG II. Pretreatment with ANG II receptor antagonists, L-158,809 (AT1 selective) or saralasin, blocked the L-162,313-induced increase in MAP. Enalaprilat, an angiotensin-converting enzyme inhibitor, failed to block the MAP response to L-162,313. In vitro, L-162,313-activated phosphoinositide turnover in rat aortic smooth muscle cell cultures was also blocked by L-158,809 and losartan (DuP-753). Therefore, L-162,313 is the first reported nonpeptide ANG II receptor agonist.

Angiotensin II↗
PubMed1995

Altered beta-adrenergic and cholinergic pulmonary vascular responses after total cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) is often followed by pulmonary hypertension, but the effects of extracorporeal circulation on vascular reactivity remain largely unknown. In this study, the influence of total CPB (t-CPB) on beta-adrenergic and cholinergic receptor-mediated pulmonary microvascular responses was examined. Sheep were placed on t-CPB without ventilation. After 90 min, sheep were separated from t-CPB and the lungs were perfused normally for 60 min. Pulmonary artery infusion of acetylcholine (muscarinic cholinergic agonist, ACh) increased pulmonary vascular resistance significantly more and isoproterenol (beta-adrenergic agonist, Iso) decreased pulmonary vascular resistance less after than before t-CPB. The response to sodium nitroprusside (SNP, guanylate cyclase activator) was similar before and after t-CPB. Relaxations (in vitro) of isolated pressurized (20 mmHg) microvessels to Iso and ACh were markedly reduced after t-CPB. Treatment with NPC-15669 (N-[9H-(2,7,-dimethylfluorenyl-9-methoxy)carbonyl]-L-leucine) did not affect these changes in vessel reactivity, although leukocyte sequestration in the lungs was reduced with the drug. The in vitro response to forskolin (adenylate cyclase activator) and SNP was similar before and after t-CPB. Complement-activated serum caused microvessels to contract in response to ACh, but it had no effect on Iso, forskolin, or SNP responses, suggesting that activation of the alternate complement pathway causes a selective reduction in endothelium-dependent relaxation. We conclude that t-CPB impairs cholinergic and beta-adrenergic pulmonary vascular responses due to effects at the level of the transmembrane receptor or coupling to the second messenger systems.

Acetylcholine↗
PubMed1994

Immunoglobulin M and A antibodies to hepatitis C core antigen in chronic hepatitis C virus infection.

To determine the prevalence and clinical significance of IgM and IgA antibody to hepatitis C virus (HCV) core antigen in chronic HCV infection, sera from 47 patients were tested for immunoglobulin class M (IgM) and immunoglobulin A (IgA) antibody to HCV core antigen by solid-phase enzyme-linked immunoassay using a recombinant core protein (aa1-150). Results were correlated with the clinical, biochemical and histological parameters, serum HCV RNA levels (determined by branched DNA signal amplification assay), and subsequent clinical response to interferon-alpha therapy. IgM anti-HCV core was detected in 11 patients (23.4 percent). There was no correlation between the presence of IgM anti-HCV core and the clinical features (sex, age, mode of acquisition), biochemical parameters (serum ALT, AST, alkaline phosphatase, and albumin level), autoimmune markers [serum globulin levels, anti-nuclear antibody (+ at < 1:80 in 7/47 patients)], serum HCV RNA levels, subsequent response to interferon-alpha therapy, and the histological features. Immunoglobulin A anti-HCV core was not detected in any of the patients. The presence of IgM ant-HCV core in a proportion of patients with chronic HCV infection indicates that the presence of serum IgM anti-HCV core may not be unique to acute HCV infection.

Adult↗
PubMed1994

Intercellular communication is reduced by TPA and Ki-ras p21 in quiescent, but not proliferating, NRK cells.

We investigated whether the growth state of NRK cells (proliferating or quiescent by serum deprivation) affected the ability of oncogenic Ki-ras p21 and the protein kinase C activator, 12-O-tetradecanoylphorbol-13-acetate (TPA), to alter gap junctional communication. We evaluated gap junctional permeance by rate analysis of the transfer of a fluorescent dye, Lucifer Yellow, between cell pairs. We found that while the gap junctions of proliferating NRK cells were unresponsive to both TPA and to Ki-ras p21, junctional communication in quiescent cells was significantly inhibited by brief exposures to 100 ng/ml TPA. Furthermore, activity of Ki-ras p21 2 h prior to TPA exposure enhanced the inhibitory effect of TPA in quiescent cells. Junctional sensitivity to TPA was transient, with inhibition of junctional communication detected at 10 min and refractory after 60 min of continuous exposure. The suppression of junctional communication by TPA was completely prevented if the oncogenic p21 had been active for a longer period of time (48 h). The application of a phorbol ester derivative (4 alpha-PDD), which does not activate protein kinase C, did not affect the ability of quiescent cells to communicate. From these results we conclude that there is a cell-state dependence of junctional sensitivity to TPA in NRK cells and that ras p21 activity potentiates the junctional response to TPA. One interesting possibility is that this involved a cell-cycle effect.

Animals↗
PubMed1994

Role of technetium-99m planar bone scanning in the evaluation of low back pain.

The records of 1018 patients with low back pain in a tertiary spine referral practice were reviewed. One hundred thirty-nine out of 1018 (13.6%) underwent technetium-99m planar bone scanning as part of their investigation. Seventy-three out of 139 scans (52%) showed increased uptake in some area, but only 27 out of 139 (19.4%) showed increased uptake specifically in the low back. Scans consistently yielded no findings with reference to the back when the prescan diagnosis was spinal stenosis, lumbar pain syndrome, herniated nucleus pulposus, or postlaminectomy syndrome. Some scans gave positive findings in patients with a diagnosis of degenerative disc disease, pseudarthrosis, spondylolisthesis, fracture, infection, metabolic disorder, or tumor. Positive scans were generally obtained early after presentation (within 3 months) and negative scans obtained later (after 6 months), suggesting that clinical suspicion is still the main indication for early scanning. Planar bone scanning was helpful in both diagnosis and therapeutic decision-making in many conditions.

Adolescent↗
PubMed1994

Adenosine and AICA-riboside fail to enhance microvascular endothelial preservation.

Crystalloid cardioplegia may cause coronary microvascular endothelial dysfunction during cardiopulmonary bypass. The perioperative administration of either adenosine or AICA-riboside (acadesine, 5-aminoimidazole-4-carboxamide-1-ribofuranoside) has been associated with improved myocardial functional preservation and improved coronary blood flow after ischemic arrest. To examine if this enhanced recovery of myocardial function and perfusion may be related to improved endothelial preservation, pigs were placed on cardiopulmonary bypass and the hearts were arrested with plain cold, hyperkalemic (K+ = 25 mmol/L) crystalloid cardioplegia, or cardioplegic solution containing either 0.1 mmol/L adenosine or 50 mumol/L AICA-riboside, which causes the release of endogenous adenosine. AICA-riboside (375 mg) also was infused over 30 minutes before cardioplegia in the later group. After 1 hour of ischemic cardioplegia, hearts were reperfused for 1 hour while the pigs were weaned from cardiopulmonary bypass. Coronary arterioles (90 to 190 microns in diameter) from both subepicardial and subendocardial regions of the left ventricle were studied in vitro in a pressurized, no-flow state with videomicroscopy. After contraction of vessels by 25% to 40% of the baseline diameter, drugs were applied extraluminally. Relaxation of control arterioles to serotonin was slightly greater in vessels from the subendocardial region compared with vessels from the subepicardial region, and subendocardial arterioles were more affected by cardioplegia than were subepicardial vessels. In contrast, relaxations of control microvessels to bradykinin and the calcium ionophore A23187 were similar in the two transmural myocardial regions. Responses to bradykinin and A23187 were significantly and similarly reduced after ischemic arrest with plain crystalloid cardioplegia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1994

Serotonergic control of androgen-induced dominance.

The present study investigates the role of serotonergic systems in anabolic steroid-induced aggression. An animal model of aggressive dominance was used to assess the chronic effects of testosterone propionate. When rats that had become dominant following administration of testosterone propionate received serotonergic agonists with selectivity for the 5-HT1A receptor (8-OH-DPAT, buspirone, gepirone), the 5-H1B receptor (eltoprazine, TFMPP), or the 5-HT2A/2C receptor (DOM), a dose-dependent decrease in dominance was demonstrated. Pretreatment with three serotonergic antagonists (pizotyline, pirenpirone, and pindolol) blocked agonist-induced reductions in dominance in varying degrees. Nonserotonergic agonists with CNS depressant effects were also tested in dominant animals. The benzodiazepine, chlordiazepoxide, did not reduce dominance except at doses that interfered with motor behavior. The opioid agonist, morphine, dose dependently decreased dominance, but this effect was reversible with administration of the serotonergic antagonist, pirenpirone, suggesting the antidominant effect of morphine had a serotonergic component. Biochemical experiments demonstrated that following chronic testosterone propionate, there was a decrease in levels of 5-HT and 5-HIAA in the hippocampus but not in the striatum or the frontal cortex. Chronic testosterone propionate also caused an increase in the affinity of [3H]8-OH-DPAT for the 5-HT1A receptor but no corresponding change in the density of 5-HT1A binding sites in the hippocampus. There was also no change in the properties of the 5-HT2 receptor in the frontal cortex following chronic testosterone propionate. These data suggest that serotonergic systems may play an important role in the control of anabolic steroid-induced aggressive dominance.

Aggression↗
PubMed1994

Adrenergic regulation of coronary microcirculation after extracorporeal circulation and crystalloid cardioplegia.

The purpose of the present study was to examine whether adrenoceptor-mediated responses of porcine coronary resistance arteries are affected by cardioplegic arrest under conditions of extracorporeal circulation (cardiopulmonary bypass; CPB). Pigs were placed on CPB. The hearts were arrested with a cold hyperkalemic crystalloid cardioplegic solution for 1 h, then were reperfused for 1 h. In vivo and in vitro beta-adrenoceptor-mediated responses were compared before CPB and 2 min and 1 h after initiation of reperfusion. In vitro responses were studied in a pressurized no-flow state with video microscopy. Isoproterenol (0.02 micrograms.kg-1.min-1, intracoronary) increased coronary blood flow by 100 +/- 32% (P < 0.001) before CPB and cardioplegic arrest, 17 +/- 7% 2 min postcardioplegia (P < 0.01), and 71 +/- 9 (P < 0.001) after 1 h of reperfusion. Relaxation of precontracted microvessels (90-180 micron) to isoproterenol, NaF, forskolin, and adenosine was reduced after cardioplegic arrest (all P < 0.001). After 1 h of postcardiolegia-reperfusion, relaxation responses to forskolin and adenosine were completely restored, whereas the responses to isoproterenol (P < 0.05) and NaF (P < 0.10) were only partially recovered. Cardioplegic arrest and postcardioplegia-reperfusion blunted the alpha 2-adrenoceptor-mediated endothelium-dependent relaxation to clonidine (P < 0.001) but did not affect the minimal (< 4%) contractile response to the alpha 1-adrenoceptor agonist phenylephrine or the relaxation to nitroprusside. These results show that hyperkalemic cardioplegia results in the generalized defect in the beta-adrenoceptor-GS protein-adenylate cyclase pathway, which is significantly restored after reperfusion.

Adenosine↗
PubMed1994

Acidemia and hypernatremia enhance postischemic recovery of excitation-contraction coupling.

The purpose of the present study was to determine whether Na(+)-H+ and Na(+)-Ca2+ exchanges modulate postischemic recovery of excitation-contraction coupling. Experiments were performed in 43 isolated isovolumic dog hearts perfused with blood (pH 7.40, 141 mmol/L Na+, 34 degrees C, paced at 2 Hz). A 3 x 3-mm region at the left ventricular (LV) apex was loaded with aequorin for monitoring [Ca2+]i simultaneously with LV pressure. No-flow ischemia for 2 to 3 minutes was followed by 20 minutes of aerobic reperfusion with (1) unmodified control blood (141 mmol/L Na+, pH 7.40), (2) acidemic blood (141 mmol/L Na+, pH 6.60, at 0 to 3 minutes of reperfusion), (3) hypernatremic blood (149 or 157 mmol/L Na+, pH 7.40, at 0 to 20 minutes of reperfusion), or (4) hyperosmotic blood (141 mmol/L Na+ + 30 mmol/L mannitol, pH 7.40, at 0 to 20 minutes of reperfusion). Reperfusion with unmodified control blood was immediately followed by an increase in [Ca2+]i and LV systolic and diastolic pressure that persisted for 2 to 3 minutes before returning to or below baseline. Ventricular arrhythmia occurred during this period (> 80%). This transient increase of [Ca2+]i was attenuated by acidemic or hypernatremic perfusate. With acidemic or hypernatremic reperfusion, recovery of LV developed pressure at 20 minutes was more complete than with unmodified control reperfusion: acidemic blood (n = 7), 93 +/- 3% (P < .01); hypernatremic blood (149 mmol/L Na+, n = 7), 89 +/- 2% (P < .02); hypernatremic blood (157 mmol/L Na+, n = 4), 91 +/- 2% (P < .01); and unmodified control blood (n = 17), 80 +/- 2%. With hyperosmotic reperfusion, recovery of LV developed pressure at 20 minutes was not improved (82 +/- 3%). From these results we conclude that (1) an increase in intracellular Ca2+ occurs transiently after no-flow ischemia and may cause arrhythmia and decreased Ca2+ responsiveness of the contractile elements, (2) acidemic and hypernatremic reperfusion ameliorates postischemic dysfunction by preventing the increase in intracellular Ca2+, suggesting that (3) Na(+)-H+ and Na(+)-Ca2+ exchange may play important modulatory roles during reperfusion.

Animals↗
PubMed1994

Parameters of pulmonary injury after total or partial cardiopulmonary bypass.

BACKGROUND: We have established that thromboxane B2 (TX) blood levels increase across the pulmonary circulation after total cardiopulmonary bypass (CPB) but not after partial CPB. In the present study, we used the same model and examined the parameters of pulmonary injury after total or partial CPB. METHODS AND RESULTS: Fourteen anesthetized sheep were placed on total CPB (n = 7), without ventilation and with occlusion of the pulmonary artery, or partial CPB (n = 7), with ventilation and an open pulmonary artery. After 90 minutes, the sheep were separated from CPB, and the pulmonary artery was perfused normally. After 30 minutes, we elevated left atrial pressure in all sheep. Plasma TX, plasma leukotriene B4, platelet counts, white blood cell counts, and plasma protein concentration were measured before CPB and every 15 minutes after CPB for 1 hour. The right and left atrial blood samples were obtained simultaneously. Pulmonary arterial pressure, left atrial pressure, and pulmonary arterial flow were measured. Pulmonary vascular resistance (PVR) was calculated for 30 minutes after CPB. Lung lymph protein, TX, leukotriene B4, and flow were measured before CPB and every 30 minutes after CPB for 1 hour. Pulmonary biopsies and bronchoalveolar lavage fluid were obtained before CPB and at the end of the experiment. After total CPB, levels of TX across the pulmonary circulation increased significantly, but leukotriene B4 remained constant. Platelets and white blood cells were consumed across the pulmonary circuit after total CPB but not after partial CPB. PVR increased by 170%, lymph flow increased by 233%, lung water content increased by 15%, and the ratio of lymph to plasma protein decreased by 20% after total CPB, but similar changes did not occur after partial CPB. CONCLUSIONS: During total CPB, the lungs are totally dependent on oxygen supply provided by nonpulsatile bronchial arterial flow. Lung injury seen with restoration of pulmonary artery flow and ventilation may be the result of an inflammatory response associated with TX elevation after a period of relative pulmonary ischemia. Pulmonary injury was not seen after less severe pulmonary arterial flow deprivation, with maintenance of ventilation (partial CPB). Although the specific cause is undetermined from these data, the occurrence of elevated TX levels and lung damage after total CPB is clearly established.

Animals↗
PubMed1994

Pulmonary microvascular responses to protamine and histamine. Effects of cardiopulmonary bypass.

Total cardiopulmonary bypass with associated reduced pulmonary blood flow causes significant alterations of endothelium-dependent pulmonary microvascular responses after resumption of normal perfusion. To determine if this change in pulmonary vascular reactivity may influence the responses of pulmonary arterioles to protamine and histamine, we examined isolated pulmonary microvessels after cardiopulmonary bypass. Sheep were heparinized, cannulated, and placed on either total bypass without ventilation or partial bypass (70% of baseline pulmonary arterial flow) with continued ventilation. After 90 minutes, sheep were separated from cardiopulmonary bypass and the lungs were perfused normally for 60 minutes. Vessels from noninstrumented sheep were used as controls. Peripheral pulmonary arterioles (90 to 190 microns) were cannulated, pressurized (20 mm Hg) in a no-flow state, and examined with video microscopy. After precontraction of vessels with the thromboxane A2 analog U46619 by 18% to 25% of the baseline diameter, vasoactive agents were applied. Protamine sulfate, histamine, heparin, and the protamine-heparin complex caused significant dose-dependent relaxations of control pulmonary microvessels. These relaxation responses were substantially reduced or converted to contractile responses in endothelium-denuded vessels, which suggests that these relaxations are mediated through endothelium-dependent mechanisms. After partial bypass, responses to protamine and histamine were slightly reduced compared with the respective responses of control vessels, whereas the relaxation to protamine-heparin complex was not significantly altered. After total bypass, relaxation responses to protamine and protamine-heparin complex were markedly reduced, whereas histamine induced contraction of pulmonary microvessels. Endothelium-independent relaxation to sodium nitroprusside was not affected by partial cardiopulmonary bypass and was slightly reduced after total bypass. A reduced direct vascular relaxation response to protamine and increased contractile response to histamine (or other humoral substances released during the systemic administration of protamine sulfate) may contribute to the elevation of pulmonary vascular resistance during infusion of protamine after cardiopulmonary bypass.

Animals↗
PubMed1994

Chronic ethanol exposure inhibits ATP-stimulated but not KCl-stimulated dopamine release in PC 12 cells.

The functional significance of the ethanol-induced alterations in intracellular concentration of free calcium ([Ca++]i) was determined in PC 12 cells by measuring agonist-stimulated dopamine (DA) release after ethanol exposure. ATP and KCl produced a concentration-dependent release of DA, which was linearly related to the net increase in [Ca++]i, but different relationships were observed with ATP and KCl. Acute addition of 150 mM ethanol inhibited KCl-stimulated release of DA, but did not alter the response to ATP. In contrast, a 4-day exposure to 150 mM ethanol led to a reduction in ATP-evoked DA release without altering the response to KCl. Furthermore, a 7-day treatment with 25 mM ethanol also decreased the response to ATP. Acute and chronic ethanol exposures, however, did not alter the relationships between DA release and the increase in [Ca++]i observed with ATP and KCl. The data indicate that acute and chronic ethanol treatments have differential effects on the responses to extracellular ATP and KCl and alter DA release primarily by altering the calcium influx stimulated by agonists.

Adenosine Triphosphate↗
PubMed1994

Micromolar levels of intracellular calcium reduce gap junctional permeability in lens cultures.

PURPOSE: To investigate in bovine and embryonic chicken lens cultures the effects of elevated intracellular calcium on the permeability of gap junctions. To determine the changes in intracellular calcium using fura-2. To detect any changes in the phosphorylation of connexin43 after ionophore treatment. METHODS: Lucifer yellow was micro-injected into individual cells, and dye spread to neighboring cells was evaluated. Intracellular calcium levels were measured using the calcium indicator, fura-2. Cultures were also labeled with 32P-orthophosphate followed by immunoprecipitation with antibodies specific for the gap junction protein, connexin43. RESULTS: Bovine lens cultures incubated in the presence of either A23187 or ionomycin showed a reduction in intercellular dye transfer. The intracellular calcium concentrations in bovine cells were increased from a mean value of 0.11 +/- .009 microM in the controls to a mean of 0.40 +/- .073 microM with ionomycin treatment. Subsequent addition of EGTA to the medium decreased the intracellular calcium concentrations to a mean of 0.26 +/- .113 microM and reversed the inhibition of dye spread found with ionomycin. With ionomycin in the medium, the phosphorylated form of connexin43 was not as prominent as in the controls. In contrast, these same treatments had no detectable effect on junctional permeability in the embryonic chicken lens cultures. Dye spread was equally extensive and rapid under control and ionophore conditions, even though fura studies showed an elevation in intracellular calcium levels. CONCLUSIONS: In the bovine cultures, physiologically relevant changes in the levels of cytoplasmic calcium markedly reduced dye transfer. The increase in cytoplasmic calcium was correlated with a change in the phosphorylation level of connexin43. The regulation of junctional communication in the chick lens cultures appears to differ significantly from that in the bovine system.

Animals↗
PubMed1993

Molecular cloning and characterization of the human A3 adenosine receptor.

The human A3 adenosine receptor was cloned from a striatal cDNA library using a probe derived from the homologous rat sequence. The cDNA encodes a protein of 318 amino acids and exhibits 72% and 85% overall identity with the rat and sheep A3 adenosine receptor sequences, respectively. Specific and saturable binding of the adenosine receptor agonist N6-(4-amino-3-[125I]iodobenzyl)adenosine [125I]ABA was measured on the human A3 receptor stably expressed in Chinese hamster ovary cells with a Kd = 10 nM. The potency order for adenosine receptor agonists was N-ethylcarboxamidoadenosine (NECA) > or = (R)-N6-phenyl-2-propyladenosine [(R)-PIA] > N6-cyclopentyladenosine (CPA) > (S)-N6-phenyl-2-propyladenosine [(S)-PIA]. The human receptor was blocked by xanthine antagonists, most potently by 3-(3-iodo-4-aminobenzyl)-8-(4-oxyacetate)phenyl-1-propylxanthine (I-ABOPX) with a potency order of I-ABOPX > 1,3-dipropyl-8-(4-acrylate)phenylxanthine > or = xanthine amino congener >> 1,3-dipropyl-8-cyclopentylxanthine. Adenosine, NECA, (R)- and (S)-PIA, and CPA inhibited forskolin-stimulated cAMP accumulation by 30-40% in stably transfected cells; I-ABA is a partial agonist. When measured in the presence of antagonists, the dose-response curves of NECA-induced inhibition of forskolin-stimulated cAMP accumulation were right-shifted. Antagonist potencies determined by Schild analyses correlated well with those established by competition for radioligand binding. The A3 adenosine receptor transcript is widespread and, in contrast to the A1, A2a, and A2b transcripts, the most abundant expression is found in the lung and liver. The tissue distribution of A3 mRNA is more similar to the widespread profile found in sheep than to the restricted profile found in the rat. This raises the possibility that numerous physiological effects of adenosine may be mediated by A3 adenosine receptors.

Adenosine↗
PubMed1993

Lidocaine prophylaxis in coronary revascularization patients: a randomized, prospective trial.

Life-threatening ventricular ectopy can occur after cardiac operations. The actual incidence of ventricular ectopy and the ability to prevent it by the routine prophylactic use of lidocaine hydrochloride have not been established. We performed a double-blind, randomized, prospective trial involving 109 patients undergoing elective coronary artery revascularization. Patients received either lidocaine (n = 54) or a placebo (n = 55) after separation from bypass. A Holter monitor was affixed to each patient for subsequent review, and bedside intensive-care monitors with alarms were used for "real-time" surveillance. The code was broken when potentially malignant ventricular ectopy or side effects attributable to the study drug were noted. Three lidocaine patients and 2 placebo patients were dropped from the study because of hemodynamic instability or bleeding. Of the remaining 104 patients, the code was broken in 12 (24%) of the 51 in the lidocaine group (9 for ectopy and 3 for mental status changes) and 10 (19%) of the 53 in the placebo group (all for ectopy) (p = not significant). Twenty-four-hour Holter monitor evaluation demonstrated occasional ventricular ectopy in all patients and nonsustained ventricular tachycardia in 28% in the lidocaine group and 48% in the placebo group (p = not significant). The mean number of runs of ventricular tachycardia per patient was 0.53 in the lidocaine group and 1.6 in the placebo group (p = 0.035). There were no significant differences in terms of other ventricular ectopy, morbidity, or mortality. No ventricular fibrillation occurred in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗