Biomedical subjects

J E Lowe

Publications and source records attributed to J E Lowe.

At least 109 records · Page 6Linked to original sources

PubMed1991

Pulsatile reperfusion after cardiac arrest improves neurologic outcome.

Cardiopulmonary bypass (CPB) using nonpulsatile flow (NPF) is advocated for refractory cardiac arrest. This study examined cerebral outcome after resuscitation with pulsatile flow (PF) versus NPF. Dogs arrested for 12.5 minute were reperfused with NPF (n = 11) using roller pump CPB or PF (n = 11) using mechanical biventricular cardiac massage. Pump flows were similar between groups; however early arterial pressures were greater during PF versus NPF, *p less than 0.05. Circulatory support was weaned at 60 minutes' reperfusion. Neurologic recovery of survivors (n = 16) was significantly better after PF versus NPF, *p = 0.01. The presence of brain lesions on magnetic resonance images did not significantly differ between groups at 7 days. Brain then were removed and regions examined for ischemic changes. Loss of CA1 pyramidal neurons was more severe after NPF versus PF, +p = 0.009. Ischemic changes were more frequent after NPF in the caudate nucleus (+p = 0.009) and watershed regions of the cerebral cortex (+p = 0.062), compared with PF. These results demonstrate that PF improves cerebral resuscitation when treating cardiac arrest with mechanical circulatory support (* = MANOVA with repeated measures, + = categorical data analysis.

Analysis of Variance↗

PubMed1991

Significant left ventricular contribution to right ventricular systolic function.

To examine the importance of systolic ventricular interdependence on right ventricular function, we used a unique electrically isolated right ventricular free wall preparation. Double-peaked waveforms for right ventricular pressure and pulmonary arterial blood flow occurred over a wide range of pacing intervals between the left and right ventricles. One component of the waveforms could be directly related to right ventricular free wall contraction, whereas the other component was directly related to left ventricular and septal contraction. For left ventricular pressure, the left ventricular component was significantly larger than the right ventricular free wall component (92.7 +/- 3.2 vs. 7.3 +/- 3.2% peak-to-peak value, P less than 0.01). For right ventricular pressure, the left ventricular and septal component was significantly greater than the right ventricular component (63.5 +/- 10.9 vs. 36.5 +/- 10.9% peak-to-peak value, P less than 0.05). Similarly, for pulmonary arterial blood flow, the left ventricular component was significantly greater than the right ventricular component. When right ventricular free wall pacing stopped in diastole, 68 +/- 4% of right ventricular systolic pressure and 80 +/- 4% of pulmonary flow were obtained in the subsequent beat. The results of this study indicate that left ventricular contraction is very important for right ventricular developed pressure and volume outflow.

Animals↗

PubMed1990

Left ventricular pressure effects on right ventricular pressure and volume outflow.

Massive destruction of the right ventricular free wall has been shown to cause only mild hemodynamic alterations. Further, the derivative of right ventricular (RV) pressure (P) is broad or double peaked, with one peak occurring coincidentally with peak left ventricular (LV) dP/dt. Both observations suggest a direct LV assistance to RV function. Since the ventricles contract nearly simultaneously, the relative contribution of LV to RV pump function has been difficult to determine. This LV assistance was quantified in six canine experiments using a unique electrically isolated RV preparation. While on total cardiopulmonary bypass, the RV free wall was electrically isolated from the remainder of the heart. This preparation allowed for wide variations in the timing interval between RV and LV contractions. Double-peaked waveforms for RVP and pulmonary flow (RVF) occurred over a wide range (0 to 300 ms) of pacing intervals between the RV and LV. One derivative peak always followed RV contraction for RVP and RVF (r = 0.971 +/- .011, P less than 0.01: r = 0.972 +/- .012, p less than 0.01; respectively). The second derivative peak was unrelated to the RA-RV pacing interval (r = 0.297 +/- .191, P greater than 0.5 RVP; 4 = 0.237 +/- .278, P greater than 0.5 RVF), but corresponded to the maximal LVP rise. Additionally, the magnitude of the two derivative peaks was similar when the ventricles contracted synchronously. When RV contraction preceded or followed LV contraction, the derivative peak associated with LV contraction was significantly greater (P less than 0.05, range 2.1 +/- 0.6 to 6.7 +/- 1.6 for RVP; P less than 0.05 range 1.9 +/- 0.4 to 6.7 +/- 1.5 for RVF) than the derivative associated with RV contraction. These data demonstrate a normally present, large LV assistance to RV contraction and may help to explain the RV response to myocardial infarction.

Animals↗

PubMed1990

Surgical treatment of automatic atrial tachycardias.

From 1979 to 1989, 18 patients were seen in the Electrophysiology Service, Duke University Medical Center, with automatic atrial tachycardia. There were 8 male and 10 female patients with a mean age of 28.1 +/- 2.9 years. Electrophysiological mapping localized automatic foci to right atrial sites (14 patients) and left atrial sites (4 patients). Depending on origin of the focus, patients were further diagnosed as having either chronic ectopic atrial tachycardia or inappropriate sinus tachycardia. Of the 15 patients with chronic ectopic atrial tachycardia, 6 responded to medical treatment; in 9, the tachycardia was not adequately controlled. Six of them were referred for surgical intervention. All 3 patients with inappropriate sinus tachycardia underwent operative therapy. In the surgical group of patients with chronic ectopic atrial tachycardia, all 6 had a tachycardia-induced cardiomyopathy with ejection fractions ranging from 14% to 27% (mean ejection fraction, 21% +/- 2.7%). Surgical techniques used (alone or in combination) included an isolation procedure in 1 patient, cryoablation in 4 patients, and excision of atrial appendages or portions of atrial free walls in 7. Normal sinus rhythm developed in all surgical patients except 1 patient who had intractable congestive heart failure preoperatively and died of this condition and stroke. The overall success rates for medical and surgical therapy were 33.3% and 88.9%, respectively (p less than 0.01). Long-term follow-up was possible for 7 (87.5%) of 8 patients 3 to 7 years after operation. All patients with chronic ectopic atrial tachycardia were cured, but only 1 of 3 patients with inappropriate sinus tachycardia was in sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1990

Variation in the loss of O6-methylguanine-DNA methyltransferase during immortalization of human fibroblasts.

We have examined O6-methylguanine-DNA methyltransferase (MT) activity in four human fibroblast cell lines during immortalization. Transfection of primary fibroblasts with the plasmid pSV3gpt or pSV3neo, which encode the SV40 large T antigen, confers a transformed phenotype but not immediate immortality. After a period of growth (pre-crisis) the cells enter a quiescent phase (crisis) from which an immortal clone of cells eventually grows out. From measurements of MT activity in extracts of cells taken at different defined stages of the immortalization process, we conclude that the establishment of a Mex- (MT-deficient) cell population is not specifically associated with cellular transformation or with any particular stage of immortalization. It appears that in different cell populations the change from Mex+ to Mex- may occur at different times during the immortalization process and that the change may be very abrupt.

Antigens, Polyomavirus Transforming↗

PubMed1990

Observer variation in equine abdominal auscultation.

The reliability of abdominal auscultation was investigated via an observer variation study. Clinicians listened to a variety of minute-long equine gut sound recordings. They evaluated the amount of gut sounds as 'absent', 'decreased', 'normal', or 'increased'. They subsequently evaluated the same recordings replayed in a different order. Intra- and inter-observer agreement was measured by the statistic kappa. There was significant intra-observer (kappa 0.57) agreement, but less agreement between observers (kappa 0.37). The best agreement was on the classification of sound tracks as 'absent' (intra-observer kappa 0.72 and inter-observer kappa 0.55). There was significant correlation between the clinicians' average assessment of the recordings and their acoustic energy levels. In this study abdominal noise was reliably assessed by auscultation. Standardised techniques and definitions would probably enhance the reliability of abdominal auscultation for the evaluation of gastrointestinal disease.

Abdominal Pain↗

PubMed1990

Nonpharmacologic treatment of the Wolff-Parkinson-White syndrome and other supraventricular tachycardias.

Nonpharmacologic treatment using surgery or intracardiac catheter ablation can be used for several forms of supraventricular tachycardia. Surgery is highly successful in preventing recurrent tachyarrhythmias in patients with the Wolff-Parkinson-White syndrome and can be recommended as first-line treatment in several situations. Catheter ablation of the atrioventricular conduction system combined with an implanted ventricular pacemaker can offer substantial relief to selected patients with drug-refractory atrial fibrillation. Technical advances in catheter ablation will undoubtedly lead to more widespread use of this form of therapy in supraventricular tachycardia.

Cardiac Catheterization↗

PubMed1990

Importance of preexcited QRS morphology during induced atrial fibrillation to the diagnosis and localization of multiple accessory pathways.

The present investigation evaluates the ability of several electrocardiographic (ECG) and electrophysiologic methods to identify multiple accessory pathways in 47 patients in whom the presence and sites of multiple accessory pathways were confirmed intraoperatively. To establish ECG features that suggested the presence of multiple accessory pathways in these patients, we initially studied the 12-lead ECG during maximal preexcitation in 101 patients with single accessory pathways. Distinctive 12-lead ECG patterns were noted for six defined anatomic areas around the right and left atrioventricular groove. Multiple preexcited QRS morphologies, each typical for a separate accessory pathway, and atypical preexcited QRS morphologies were recorded during atrial fibrillation in 31 of 47 (66%) patients with multiple accessory pathways. By comparison, the ECG during sinus rhythm and rapid atrial pacing identified 14 (32%) and 26 (55%) of the patients, respectively. In 12 (26%) patients in whom evidence for multiple accessory pathways was absent from endocardial mapping data, atrial fibrillation provided the diagnosis. In five (11%) patients, atrial fibrillation was the only method that demonstrated the presence of multiple accessory pathways. A combination of ECG findings during atrial fibrillation and rapid atrial pacing plus endocardial mapping data identified 43 (91%) of the patients with multiple accessory pathways. There were two unique fusion patterns on the 12-lead ECG that were characteristic of specific multiple accessory pathway combinations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Accelerated transmural gradients of energy compound metabolism resulting from left ventricular hypertrophy.

Eighteen dogs underwent transmural left ventricular biopsies for adenosine triphosphate and suturing of the noncoronary cusp, creating valvular aortic stenosis. Three months after aortic stenosis and the subsequent development of left ventricular hypertrophy, animals underwent repeat transmural left ventricular biopsies followed by total myocardial ischemia at 37 degrees C. Left ventricular tissue samples for adenosine triphosphate and lactate levels were determined at 15-minute intervals and compared with 15 control animals. No significant difference between subendocardial and subepicardial adenosine triphosphate levels was found between left ventricular samples taken before left ventricular hypertrophy and 3 months after left ventricular hypertrophy. Significant differences in adenosine triphosphate utilization occurred between subendocardial and subepicardial layers in control and left ventricular hypertrophy myocardium, however. The gradient between the subendocardium and the subepicardium was significantly increased by left ventricular hypertrophy (p less than 0.05). Significant differences also occurred within the same layer when left ventricular hypertrophy and control groups were compared. During total ischemia, lactate concentration was significantly greater within the subendocardium than within the subepicardium in left ventricular hypertrophy. The onset of ischemic contracture was 48.2 +/- 2.1 minutes in left ventricular hypertrophy versus 62.3 +/- 1.8 minutes in control hearts (p less than 0.01). Subendocardial intramyocardial pressure increased significantly earlier than subepicardial in both left ventricular hypertrophy and control hearts. Adenosine triphosphate was used, and lactate accumulated more rapidly in animals with a more pronounced hemodynamic gradient. These data show that after left ventricular hypertrophy, adenosine triphosphate stores in the subendocardium and the subepicardium are unchanged from control values, yet the rates of adenosine triphosphate utilization and lactate accumulation during total ischemia are significantly increased. Furthermore, the subendocardial to subepicardial gradient of adenosine triphosphate utilization during ischemia found in normal hearts is markedly increased by left ventricular hypertrophy.

Adenosine Triphosphate↗

PubMed1990

Mechanical myocardial actuation during ventricular fibrillation improves tolerance to ischemia compared with cardiopulmonary bypass.

Direct mechanical ventricular actuation (DMVA) is a unique non-blood-contacting biventricular assist device that provides circulatory support during ventricular fibrillation without demonstrating adverse effects on the myocardium. The purpose of this study was to assess the preservation of myocardial energy stores and myocardial responses to ischemia after circulatory support during ventricular fibrillation with direct mechanical ventricular actuation versus cardiopulmonary bypass. Twenty adult mongrel dogs were randomized to receive circulatory support with either cardiopulmonary bypass or direct mechanical ventricular actuation. After 4 hours of ventricular fibrillation, hearts were defibrillated and left ventricular transmural biopsies were obtained. Hearts were then excised and subjected to 90 minutes of normothermic total ischemia. Serial biopsies were obtained at 15-minute intervals to determine regional depletion of high energy phosphates. The time-to-peak ischemic contracture was recorded by using needle-tipped Millar catheters placed in the left ventricular endocardium, epicardium, septum, and right ventricle. Time-to-peak ischemic contracture of the endocardium (62.6 +/- 1.4 vs. 58.8 +/- 1.0 minutes, p less than 0.05) and septum (61.1 +/- 6.9 vs. 46.9 +/- 6.2 minutes, p less than 0.004) were significantly prolonged after direct mechanical ventricular actuation versus cardiopulmonary bypass, respectively. Similar trends were noted in the epicardium and right ventricular regions; however, these differences were not statistically significant. Left ventricular adenosine triphosphate (ATP) levels were better preserved after direct mechanical ventricular actuation (22 +/- 1.5 mumols/g dry wt) compared with cardiopulmonary bypass (17 +/- 1.9 mumols/g dry wt). The depletion of left ventricular endocardium ATP during normothermic ischemia was significantly delayed after direct mechanical ventricular actuation compared with cardiopulmonary bypass.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1990

Optimal temperature for preservation of donor myocardium.

The ideal method for the preservation of donor hearts for transplantation is unclear. To assess the optimal temperature for donor myocardium preservation, the recovery of isolated canine hearts (n = 20) exposed to 4 hours of either standard ice-chest hypothermia (0-4 degrees C) or constant moderate hypothermia (12 degrees C) were compared. Functional and metabolic data were acquired before hypothermia and every 30 minutes during 3 hours of reperfusion with oxygenated blood. Mean end-systolic pressure-volume slopes were 2.11 +/- 0.06 and 2.09 +/- 0.06 mm Hg/ml for ice-chest hypothermia and constant moderate hypothermia, respectively (p = NS), which were unchanged from control. All y intercepts during reperfusion were decreased compared with control (p = 0.002) without any differences between groups. End-diastolic pressures were greater than control throughout the reperfusion period for both groups (p = 0.02), but there was a difference in change of end-diastolic pressures with time between groups (p = 0.04). Dry/wet ratios were similar after preservation and reperfusion in both groups. ATP recovered to control levels during reperfusion for both groups although energy charge ratios were greater for hearts exposed to constant moderate hypothermia (p = 0.007). These data indicate that intracellular energy stores are well maintained by preservation using either technique. Changes in function appear to be related to altered compliance irrespective of preservation temperature. These data suggest that a wide range of temperatures may be acceptable for donor heart preservation.

Animals↗

PubMed1990

Mechanical cardiac actuation achieves hemodynamics similar to cardiopulmonary bypass.

The disadvantages of blood/interface interactions and difficult installation are common to current circulatory support devices. Direct mechanical ventricular actuation (DMVA) is a method of biventricular cardiac massage that avoids contact of blood with various surfaces. The purpose of this study was to compare hemodynamic responses and organ perfusion between DMVA and cardiopulmonary bypass (CPB). Twenty adult mixed-breed dogs randomized for DMVA or CPB were anesthetized with alpha-chloralose. During 4 hours of ventricular fibrillation, animals received either DMVA or CPB with aortic arch perfusion (90 to 120 ml/kg/min), bicaval venous return, and full left ventricle venting. Hemodynamics and organ perfusion were assessed by multivariant analysis of variance with repeated measures. Blood flow was similar to normal sinus rhythm (control) with either method; however, average CPB flows (control, 110%) were increased significantly over DMVA flows (control, 75%) (p = 0.016). The resulting mean arterial pressures were significantly greater during DMVA (control, 66%) compared to CPB (control, 49%) (p = 0.0011). Radiolabeled microspheres were the measure of organ perfusion during sinus rhythm and at 2 and 4 hours of circulatory support. Myocardial blood flow was equal to control in all regions during DMVA; CPB resulted in increased flows to the left ventricular epicardium, septum, and right ventricle. DMVA generated significantly greater flows to the renal cortex. All other organs demonstrated similar perfusion with either method. However, CPB displayed declining cerebral flows at 4 hours compared to DMVA (42% vs 55% control, respectively). Overall, DMVA provided hemodynamic stability equal to that of CPB. Rapid application and avoidance of blood/surface contact make DMVA a favorable method of temporary circulatory support.

Animals↗

PubMed1989

Correlates of survival in patients with postinfarction ventricular septal defect.

Prognostic indicators of survival in 42 consecutive patients (21 men and 21 women) with postinfarction ventricular septal defect were reviewed. Infarct location was anterior in 57%, inferior in 33%, and combined in 10%. The hospital mortality among 9 patients not receiving surgical therapy was 100%. Of the 33 surgically treated patients, 19 (58%) survived. Time from diagnosis to operation, ventricular function, and presence or absence of shock were analyzed in a logistic regression model to determine which factors carried independent prognostic value. Shock was independently predictive of operative mortality (p less than 0.01). Of additional variables examined, nonsurvivors were characterized by a shorter time from postinfarction ventricular septal defect to operation, a relatively higher incidence of inferior infarction, moderate right ventricular dysfunction and mild left ventricular dysfunction, and a lower right ventricular systolic pressure. Results of postmortem examination were available for 15 nonsurvivors. Quantitative analysis of percent ventricle infarcted revealed that in patients with inferior infarctions, a mean of 31% of the right ventricle was infarcted compared with 10% in patients with anterior infarction (p = 0.059). Kaplan-Meier survival estimates revealed 1-year survival of 70%, 5-year survival of 55%, and 10-year survival of 20%. Seventy percent of survivors were in New York Heart Association class I or II. These data show that, irrespective of ventricular function or timing of operation, the development of shock is the most important predictor of survival in postinfarction ventricular septal defect. The higher mortality in patients with inferior infarction may be associated with a greater degree of right ventricular infarction and consequent dysfunction. Finally, long-term survival and excellent functional recovery can be achieved in patients undergoing operation.

Aged↗

PubMed1989

Properties of N-methyl-N-nitrosourea-resistant, Mex- derivatives of an SV40-immortalized human fibroblast cell line.

We have selected two N-methyl-N-nitrosourea (MNU)-resistant derivatives of the SV40-transformed, alkyltransferase-deficient (Mex-) human fibroblast cell line MRC5V1. Both derivatives remain Mex-. They are cross-resistant to methylmethanesulphonate (MMS) and 6-thioguanine (6TG) but not 2,6-diaminopurine. They show increased sensitivity to the bifunctional chloroethylating agent mitozolomide (MTZ). We have transfected MRC5V1 and one of our MNU-resistant lines with the bacterial O6-methylguanine (O6-MeG)-DNA methyltransferase (ada) gene. Transfectants of MRC5V1 are significantly more resistant to MNU but exhibit only a small increase in resistance to MMS and MTZ. Transfectants of the MNU-resistant derivative exhibit only a small additional increase in resistance to MNU, no further increase in resistance to MMS and a large increase in resistance to MTZ. The pattern of resistance to cytotoxic agents of these transfectants suggests that a second mechanism of resistance to MNU, independent of alkyltransferase expression, is operating in our resistant lines. This mechanism apparently enables the cells to tolerate O6-MeG and 6TG, but not chloroethyl adducts in their DNA.

Carcinogens↗

PubMed1989

Impaired recovery and mutagenic SOS-like responses in ataxia telangiectasia cells.

Radiosensitive fibroblasts from patients with ataxia telangiectasia (AT) were studied for their proficiency in two putative eukaryotic SOS-like responses, namely the enhanced reactivation (ER) and enhanced mutagenesis of damaged viruses infecting pre-irradiated versus mock-treated cells. A previous report indicated that, unlike normal human cells, a line of AT fibroblasts (AT5BIVA) could not be induced to express ER of damaged parvovirus H-1, a single-stranded DNA virus, by UV- or X-irradiation. In the present study, AT5BIVA fibroblasts were also distinguished from normal cells by the inability of the former to achieve enhanced mutagenesis of damaged H-1 virus upon cell UV-irradiation. In contrast, dose-response and time-course experiments revealed normal levels of ER of Herpes simplex virus 1, a double-stranded DNA virus, in X- or UV-irradiated AT5BIVA cells. Taken together, these data point to a possible deficiency of AT cells in a conditioned mutagenic process that contributes to a greater extent to the recovery of damaged single-stranded than double-stranded DNA. Such a defect may concern the replication of damaged DNA or the generation of signals promoting the latter process and may be related to the lack of radiation-induced delay that is typical of AT cell DNA synthesis.

Ataxia Telangiectasia↗

PubMed1989

Four digital algorithms for activation detection from unipolar epicardial electrograms.

The reproducibility of activation detection by each of four algorithms used to calculate maximum derivatives was tested on two sequential paced beats of right ventricular unipolar epicardial electrograms which represented either local activation of the right ventricle alone or synchronous activation of both ventricles. The methods were evaluated by comparing the shape of the two beats aligned on their selected activation times, i.e., the time at which the maximum negative deflection occurred, the differences in activation intervals for the two beats, and the effect on the activation time of superimposing distant events on local activation. The 17-point second-order data fit algorithm performed slightly better than the first-order difference, three-point Lagrange derivative, and five-point second-order data fit algorithms except that activation time selection by the 17-point technique was slightly, but significantly, delayed by the superposition of distant potentials. The 17-point second-order data fit technique is therefore recommended for use in detecting activation unless computation time is a major consideration. In that case, the five-point second-order data fit technique, which uses only four data values for each computation, can be used with only slight decreases in accuracy.

Algorithms↗

PubMed1989

Interpolating unipolar epicardial potentials from electrodes separated by increasing distances.

In cardiac mapping, potentials for unexplored areas are estimated by interpolating values from nearest neighbor electrodes regardless of distances between these sites or wave front orientation. The effects of these variables on interpolated unipolar electrograms were analyzed two ways: with a computer model and with electrograms recorded 9.9 and 14.1 mm apart. For the model, wave fronts (n = 39) were generated from electrograms recorded during right ventricular (RV) activation in five dogs following the RV isolation procedure. Each wave front was assumed to propagate radially at 0.5 m/sec from a site 30 mm from the center of a square array with electrodes located at the center and corners. Each wave front crossed the array with its tangent at an angle of 0 degrees, 45 degrees, or 90 degrees to the diagonal line connecting opposite corner electrodes. Potentials for all five sites were generated from each wave front and were interpolated for the center site from the generated corner potentials. Generated and interpolated center site potentials were compared using correlation coefficients (r) and percent root mean square differences (%RMSD). Mean r values fell below 0.90 for interelectrode distances of 15.6 mm, 2.8 mm, and 1.4 mm at 0 degrees, 45 degrees, and 90 degrees wave front orientations, respectively. For experimentally measured potentials recorded 9.9 mm apart, results from interpolated electrograms were similar to results from the model at 0 degrees propagation. Electrograms interpolated from potentials measured 14.1 mm apart had poorer r and %RMS values than those from the computer model. Thus, with linear interpolation unipolar electrograms can be inaccurately interpolated from electrodes less than 3 mm apart or correctly interpolated from electrodes more than 14 mm apart depending upon wave front orientation.

Action Potentials↗

PubMed1989

Current management of mitral valve incompetence associated with coronary artery disease.

At a time when hospital mortality for adult cardiac operations is continuing to fall, the combined mitral valve coronary bypass subset remains at relatively high risk. Efforts to improve results should be directed toward a more general application of mitral reconstruction in this population, tailoring the type of repair to the pathological anatomy of valve dysfunction. Other promising therapeutic measures include the liberal use of reperfusion therapy in the acute papillary muscle dysfunction group, better selection patients for operation, and perhaps operative recommendation to a greater proportion of the more stable patients that previously were treated medically. Finally increasing the general awareness of this problem should hasten the development of improved management strategies.

Coronary Artery Bypass↗