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R G Johnson

Publications and source records attributed to R G Johnson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Atrial fibrillation after minimally invasive coronary artery bypass grafting: A retrospective, matched study.

BACKGROUND: Atrial fibrillation after cardiac operations is a source of morbidity and resource consumption. Various factors common to cardiac operations have been cited as causal. Comparison of the incidences of atrial fibrillation after conventional cardiac operations and minimally invasive cardiac operations may provide some insight into the mechanisms of this complication. METHODS: All patients undergoing minimally invasive direct coronary artery bypass grafting from January 26, 1996, through September 17, 1997, were evaluated for the occurrence of in-hospital postoperative atrial fibrillation. Data from these 55 patients were compared with data from a control cohort of patients undergoing conventional, solitary coronary artery bypass grafting. Each patient undergoing minimally invasive direct coronary artery bypass grafting was matched by age (+/- 3 years) and date of operation (+/- 7 days) with a patient undergoing conventional coronary artery bypass grafting. RESULTS: During the period since the advent of minimally invasive direct coronary artery bypass grafting at our institution, the incidence of postoperative atrial fibrillation has been slightly lower among the patients undergoing this form of coronary artery bypass grafting (26%) than among the total population of patients undergoing conventional coronary artery bypass grafting (34%). Comparison of the age-matched groups, however, showed the incidence to be slightly but not significantly greater in the minimally invasive direct coronary artery bypass grafting cohort (13/55, 24%) than in the conventional coronary artery bypass grafting cohort (11/55, 20%; P =. 6). The minimally invasive direct coronary artery bypass grafting group was less likely to be discharged with antiarrhythmic therapy than was the conventional coronary artery bypass grafting group (6 versus 10; P =.006). CONCLUSIONS: According to these data, mechanisms traditionally implicated in atrial fibrillation after coronary artery bypass grafting, such as the use of cardiopulmonary bypass, mechanical manipulation of the atrium, and atrial ischemia, are not causal but may be related to the duration of the arrhythmic complication. Strategies directed toward management and reduction of the incidence of postoperative atrial fibrillation should be focused accordingly.

Age Distribution↗
PubMed1999

Echocardiographic predictors of left ventricular outflow tract obstruction and systolic anterior motion of the mitral valve after mitral valve reconstruction for myxomatous valve disease.

OBJECTIVE: To determine predictors of systolic anterior motion and left ventricular outflow tract obstruction (SAM/LVOTO) after mitral valve repair (MVRep) in patients with myxomatous mitral valve disease. BACKGROUND: Mechanisms for the development of SAM/LVOTO after MVRep have been described; however, predictors of this complication have not been explored. We hypothesize that pre-MVRep transesophageal echocardiography (TEE) can predict postrepair SAM/ LVOTO. METHODS: Using TEE, the lengths of the coapted anterior (AL) and posterior (PL) leaflets and the distance from the coaptation point to the septum (C-Sept) were measured before and after MVRep in 33 patients, including 11 who developed SAM/LVOTO (Group 1) and 22 who did not (Group 2). RESULTS: Group 1 patients had smaller AL/PL ratios (0.99 vs. 1.95, p < 0.0001) and C-Sept distances (2.53 vs. 3.01 cm, p = 0.012) prior to MVRep than those in Group 2. Resolution of SAM/LVOTO was associated with increases in AL/PL ratio and C-Sept distance. This reflects a more anterior position of the coaptation point in those who developed SAM/ LVOTO. CONCLUSIONS: These data suggest that TEE analysis of the mitral apparatus can identify patients likely to develop SAM/LVOTO after MVRep for myxomatous valve disease. The findings are consistent with the concept that SAM of mitral leaflets is due to anterior malposition of slack mitral leaflet portions into the LVOT. The position of the coaptation point of the mitral leaflets is dynamic and a potential target and end point for surgical designs to prevent SAM/LVOTO post MVRep.

Aged↗
PubMed1999

Overexpression of thyroid hormone receptor alpha 1 during zebrafish embryogenesis disrupts hindbrain patterning and implicates retinoic acid receptors in the control of hox gene expression.

Nuclear receptors play key roles in anterior/posterior (A/P) axis formation during vertebrate embryogenesis. Within this gene family, retinoic acid receptors and retinoic acid itself have profound influences on the establishment of the A/P axis. Thyroid hormone receptors are expressed during early periods of development, long before the establishment of the thyroid gland, and are able to interact with retinoic acid receptors. Here we examined the ability of the thyroid hormone receptor alpha 1 to affect early embryonic development by mRNA injection of either repressor or activator forms of the thyroid hormone receptor. Overexpression of either the thyroid hormone receptor alpha 1 or a constitutive repressor form, v-erbA, caused a swelling in the rostral hindbrain. These defects were associated with disorganization and loss of rhombomere borders as well as an increase in the number of acetylcholine esterase positive cells. This phenotype correlated with a reduction in hoxa1 expression during gastrulation. Furthermore, injection of either thyroid hormone receptor alpha 1 or v-erbA mRNA repressed a reporter gene that contained a retinoic acid response element, demonstrating the ability of the thyroid hormone receptor alpha 1 to repress retinoic acid signaling during gastrulation. In contrast, embryos treated with retinoic acid alone or embryos injected with thyroid hormone receptor alpha 1 and treated with the thyroid hormone analog TRIAC displayed a similar set of defects, including loss of the midbrain-hindbrain border and severe disruption of the rostral hindbrain. These studies support the involvement of retinoic acid and its receptors in the direct control of Hox gene expression and the early patterning of the zebrafish central nervous system.

Animals↗
PubMed1999

Potassium concentrations and ventricular ectopy: a prospective, observational study in post-cardiac surgery patients.

OBJECTIVE: To determine whether a correlation exists between concentrations of intracellular and extracellular potassium and to determine the frequency of ventricular ectopy in patients after cardiac operations. DESIGN: Prospective, observational clinical evaluation. SETTING: Surgical-respiratory intensive care unit of a university-affiliated tertiary care center. PATIENTS: Continuous 24-hr electrocardiographic monitoring was performed, and serum (extracellular) and erythrocyte (intracellular) potassium concentrations ([K+]e and [K+]i) were determined, before cardiopulmonary bypass, immediately postoperatively, and at 2, 4, 12, and 20 hrs after elective coronary bypass grafting in 31 patients. INTERVENTIONS: None. Potassium replacement was left to the discretion of the attending physicians. MEASUREMENTS AND MAIN RESULTS: Although the mean [K+]e varied significantly during the postoperative 24-hr period (p<.0001), the [K+]i did not (p = .953). No significant correlations were found between premature ventricular beats and [K+]i, [K+]e, or [K+]i/[K+]e (all p>.05). However, among the few patients who had one or more episodes of ventricular tachycardia (VT) within 30 mins of a study K+ sample, the mean [K+]e was significantly lower during the episode(s) of VT compared with the mean [K+]e in the absence of VT (p<.01). CONCLUSIONS: Although it is clear that over the clinically acceptable range of [K+]e and [K+]i concentrations seen in this population, there is no correlation between potassium concentrations and the occurrence of premature ventricular beats, the infrequent association of more serious ventricular ectopy, VT, with lower [K+]e concentrations supports the practice of using serum potassium to guide potassium replacement in patients after cardiac operations.

Coronary Artery Bypass↗
PubMed1999

Surgical ICU recidivism after cardiac operations.

BACKGROUND: Decreasing the ICU length of stay (LOS) after cardiac operations may increase ICU recidivism, obviating the benefit of early discharge. METHODS: From January 1, 1994 to January 1, 1998, there were 2,388 consecutive cardiac operations, from which 2,228 patients were discharged alive from the ICU and had sufficient information to determine their incidence of ICU return, the reasons for their return, their ICU LOS (initial and secondary LOS), and mortality. RESULTS: A decrease occurred in the initial ICU LOS from 1994 through 1997 (medians for 1994, 1995, 1996, and 1997, respectively: 31 h, 26.4 h, 24.5 h, and 24 h; and means, respectively: 69.4 +/- 139.8, 62.8 +/- 114.1, 52.5 +/- 104.0, and 56.2 +/- 103.4 h; p = 0.048). In association with this, however, ICU recidivism increased (as percentage of discharges, respectively: 3.9%, 4.2%, 6.1%, and 8.4%; p = 0.005). Inclusive of secondary ICU LOS, the total ICU LOS hours still decreased over the 4-year period. Most notably, the incidence of readmission increased with longer initial LOS (initial LOS quartiles from shortest to longest: 3.9%, 5.2%, 4.7%, and 9.2%; p = 0.0008). Predictors of ICU recidivism included preoperatively, a history of congestive heart failure, and a lower mean left ventricular ejection fraction (52.7 +/- 19.3% vs 49.8 +/- 21.5%; p = 0.0080); and, postoperatively, an increased mean weight gain (8.5 +/- 5.6 kg vs 10.3 +/- 4.7 kg; p = 0.040) and longer mean initial ventilator time (157 +/- 299 h vs 35 +/- 107 h; p = 0.038). The most common reason for readmission was pulmonary problems. CONCLUSIONS: Over the years studied, the initial ICU LOS after cardiac operations has decreased in association with a significant increase in ICU recidivism. Importantly, however, patients readmitted to the ICU are those with longer initial LOSs. Decreased initial stay does not account for our increased ICU recidivism, and efforts to decrease ICU recidivism can focus on the patients with poor preoperative cardiac function and longer initial ICU stays.

Aged↗
PubMed1998

Structural studies on phospholamban and implications for regulation of the Ca(2+)-ATPase.

The cardiac sarcoplasmic reticulum (SR) protein phospholamban (PLB) is an endogenous inhibitor of the SR Ca(2+)-ATPase. Phosphorylation of PLB relieves this inhibition and up-regulates calcium transport. PLB has proved remarkably difficult to study by conventional solution-state nuclear magnetic resonance (NMR) methods, due primarily to the extreme hydrophobic nature of the protein and its propensity to form pentamers. That the C-terminal domain of PLB is helical and membrane spanning is now well established; the structure of the cytoplasmic domain is relatively ill defined. In order to discern the effect of phosphorylation on the structure of the cytoplasmic domain, we have characterized a variety of model peptides in several structure-inducing and/or lipid-mimicking environments using circular dichroism and solution-state NMR. The resolution of peptide structures obtained in aqueous trifluoroethanol was markedly improved by the incorporation of 15N labels into the peptide backbone, allowing a variety of isotope edited, filtered, and resolved techniques to be applied. Molecular dynamics simulations on the full-length protein were combined with an analysis of published data to suggest a revised model for the structure of PLB.

Amino Acid Sequence↗
PubMed1998

Pharmacology of the cardiac sarcoplasmic reticulum calcium ATPase-phospholamban interaction.

Accumulating evidence points to the critical role of phospholamban (PLB) regulation of the cardiac sarcoplasmic reticulum (SR) calcium ATPase in influencing the kinetics of calcium handling within the cardiac myocyte under normal and pathological conditions. Based on the data, it has been hypothesized that PLB inhibitors (e.g., calcium ATPase stimulators) would be of potential importance as positive lusitropes and inotropes in the treatment of heart failure. Experiments measuring tension transients in saponin-permeabilized cardiac muscles from genetically engineered mice under a variety of SR calcium loading conditions provide evidence of the functional alterations that can be achieved by manipulation of the degree of PLB inhibition of the calcium pump. Testing of the above hypothesis will ultimately require a selective, high-affinity, membrane-permeable small molecule stimulator of the cardiac calcium pump. Screening for cardiac calcium pump activators has produced a series of agents exerting apparently different mechanisms of action; some may be tools to help to elucidate the nature of the PLB-calcium ATPase interaction(s). The rationale for PLB as a drug target, the optimal profile of a PLB inhibitor, and the properties of several low-molecular-weight compounds will be explored.

Animals↗
PubMed1998

Evidence that dorsal-ventral differences in gap junctional communication in the early Xenopus embryo are generated by beta-catenin independent of cell adhesion effects.

Gap junctional communication (GJC) is regulated in the early Xenopus embryo and quantitative differences in junctional communication correlate with the specification of the dorsal-ventral axis. To address the mechanism that is responsible for regulating this differential communication, we investigated the function of beta-catenin during the formation of the dorsal-ventral axis in Xenopus embryos by blocking its synthesis with antisense oligodeoxynucleotides. This method has previously been shown to reduce the level of beta-catenin in the early embryo, prior to zygotic transcription, and to inhibit the formation of the dorsal axis (Heasman et al., 1994, Cell 79, 791-803). We show here that antisense inhibition of beta-catenin synthesis also reduces GJC among cells in the dorsal hemisphere of 32-cell embryos to levels similar to those observed among ventral cells. Full-length beta-catenin mRNA can restore elevated levels of dorsal GJC when injected into beta-catenin-deficient oocytes, demonstrating the specificity of the beta-catenin depletion with the antisense oligonucleotides. Thus, endogenous beta-catenin is required for the observed differential GJC. This regulation of GJC is the earliest known action of the dorsal regulator, beta-catenin, in Xenopus development. Two lines of evidence, presented here, indicate that beta-catenin acts within the cytoplasm to regulate GJC, rather than through an effect on cell adhesion. First, when EP-cadherin is overexpressed and increased adhesion is observed, embryos display both a ventralized phenotype and reduced dye transfer. Second, a truncated form of beta-catenin (i.e., the ARM region), that lacks the cadherin-binding domain, restores dorsal GJC to beta-catenin-depleted embryos. Thus, beta-catenin appears to regulate GJC independent of its role in cell-cell adhesion, by acting within the cytoplasm through a signaling mechanism.

Animals↗
PubMed1998

Low-dose dopexamine's effect on lung and gut function after CPB in a sheep model.

OBJECTIVE: The lung injury regularly associated with cardiopulmonary bypass (CPB) may be linked to gut mucosal dysfunction occurring as the result of mucosal ischemia associated with nonpulsatile CPB. To examine this possibility we postulated that the weak-beta 2 agonist dopexamine would improve gut mucosal blood flow, thereby decreasing gut and lung dysfunction seen after CPB in sheep. METHODS: Anesthetized sheep had 2 h of hypothermic (24 degrees C), nonpulsatile CPB, and 60 min of cold, blood cardioplegic arrest. After warming they were separated from CPB for 2 h of reperfusion. Before and during CPB, dopexamine at 2 micrograms/kg/min (n = 7) or saline (n = 7) were infused in a blinded fashion. Hemodynamic parameters were measured. Biatrial thromboxane B2 levels were obtained. Mesenteric arterial flow (QSMA), mucosal flow (Qmuc), FD-4 clearance (ClFD-4), and tonometric pHi were measured at baseline and 30-min intervals on, and after, CPB. RESULTS: After CPB, similar reductions in MAP were seen (P < 0.05 vs. baseline), but heart rate and the mean pulmonary vascular resistance were significantly increased in the dopexamine animals (P < 0.05 vs. placebo). Plasma thromboxane was similarly increased in both groups after CPB (P < 0.05 vs. baseline), returning to baseline 1 h after CPB. The Qsma was not altered, but a statistically significant decrease in Qmuc and pHi occurred in both groups (P < 0.05 vs. baseline). In both groups FD-4 clearance reached a peak 30 min after CPB (P < 0.05; dopexamine vs. baseline). After 2 h neither of these changes returned to control levels. CONCLUSIONS: In this ovine model, gut mucosal ischemia and increased permeability occur with hypothermic CPB, but dopexamine administration during CPB, compared to placebo, neither ameliorates these intestinal derangements nor reduces post-CPB lung pathophysiology.

Adrenergic beta-Agonists↗
PubMed1998

Kainic acid lesions in adult rats as a model of schizophrenia: changes in auditory information processing.

Previous studies have suggested that intracerebroventricular kainic acid injections alter brain anatomy and neurochemistry in a manner similar to what is observed in schizophrenic patients. Disturbances in sensory information processing are one of the major symptoms of schizophrenia. Thus, the present experiments were designed to evaluate the hypothesis that hippocampal damage, induced by administration of kainic acid, would alter the processing of auditory stimuli in a paired-click paradigm. Adult male Sprague-Dawley rats were implanted for surface recording of auditory evoked potentials. At the time of electrode implantation, the rats also received bilateral injections of either kainic acid or the vehicle solution. In vehicle-treated rats, the midlatency N40 component of the auditory evoked potential was diminished in amplitude by approximately 60% in response to the second of a pair of clicks delivered 0.5 s apart. By contrast, no reduction of the N40 wave evoked by the second click was observed in kainate-treated rats. Further, administration of haloperidol, a prototypical neuroleptic agent, did not improve this auditory processing dysfunction in kainate-treated animals. Loss of auditory filtering in the paired-click paradigm and a lack of response to haloperidol in this test are typically observed in schizophrenic humans. Thus, the present results demonstrate that kainate-lesioned rats possess a functional schizophrenia-like abnormality, further reinforcing the utility of this model system for studying the basic neurobiology of schizophrenia-induced sensory processing deficits.

Acoustic Stimulation↗