Biomedical subjects

K A Kirk

Publications and source records attributed to K A Kirk.

At least 37 records · Page 2Linked to original sources

PubMed1995

Expression of PAI-1, t-PA and u-PA in cultured human umbilical vein endothelial cells derived from racial groups.

To determine whether inherent fibrinolytic differences may exist in racial groups (black americans, BA vs. white americans, WA), 55 different individual racially-derived human umbilical vein endothelial cell (HUVEC) cultures (35 BA and 20 WA) were analyzed in terms of their fibrinolytic protein (t-PA, u-PA and PAI-1) antigen and mRNA levels. Values (mean +/- SD) for measured fibrinolytic component levels include: cell-associated t-PA antigen (ELISA), 1.14 +/- 0.82 ng/ml/8.6 x 10(5) cells/24 hr in BA and 0.70 +/- 0.85 ng/ml in WA (p = 0.0624); secreted t-PA antigen, 18.65 +/- 17.06 ng/ml in BA and 10.37 +/- 6.38 ng/ml in WA (p = 0.0422); t-PA/cyclophilin mRNA ratios (Northern blot analysis), 1.90 +/- 1.34 in BA and 1.32 +/- 0.70 in WA (p = 0.0776); cell-associated PAI-1 antigen, 71.10 +/- 30.16 ng/ml/8.6 x 10(5) cells/24 hr in BA and 108.85 +/- 56.89 ng/ml in WA (p = 0.0022); secreted PAI-1 antigen, 1,582.13 +/- 612.67 ng/ml in BA and 1,992.17 +/- 711.50 ng/ml in WA (p = 0.0285); 2.4 kb PAI-1/cyclophilin mRNA ratios, 0.59 +/- 0.39 in BA and 0.79 +/- 0.31 in WA (p = 0.1085); 3.4 kb PAI-1/cyclophilin mRNA ratios, 0.70 +/- 0.47 in BA and 0.77 +/- 0.54 in WA (p = 0.6322). These combined data suggest that cultured HUVECs from BA express significantly higher levels of t-PA, lower levels of PAI-1 and approximately 1.72-fold lower molar ratio of PAI-1/t-PA antigen (183.99 +/- 168.81 vs. 315.92 +/- 164.99) (p < 0.05) than cultured HUVECs from WA, presumably reflecting an apparent inherent increased fibrinolytic potential in cultured HUVEC derived from BA.

Black People↗

PubMed1995

Xanthine oxidase inactivation attenuates postocclusion shock after descending thoracic aorta occlusion and reperfusion in rabbits.

"Declamping shock" is observed after aortic crossclamping, with hypovolemia, hypotension, and metabolic acidemia invariably present. We hypothesized that oxidants derived from xanthine oxidase influence the resuscitative interventions required to maintain baseline hemodynamic and acid-base status after aortic occlusion and reperfusion in rabbits. We also hypothesized that inactivation of xanthine oxidase with sodium tungstate could reduce systemic injury as assessed by the release of lactate dehydrogenase and alkaline phosphatase. To test these hypotheses, we established aortic occlusion in rabbits (n = 10, standard diet; n = 8, tungstate diet) for 40 minutes by inflation of a 4F Fogarty catheter in the descending thoracic aorta followed by 2 hours of reperfusion. Sham-operated rabbits (n = 10, standard diet; n = 9, tungstate diet) served as controls. Tungstate-pretreated rabbits required significantly less Ringer's solution (28%), phenylephrine (68%), and sodium bicarbonate (30%) during reperfusion (p < 0.005). Lactate dehydrogenase and alkaline phosphatase release during reperfusion was significantly attenuated by tungstate pretreatment (p < 0.05). Tungstate pretreatment resulted in plasma xanthine oxidase activities significantly lower than those in the sham group administered a standard diet (p = 0.007). Resuscitation requirements and systemic injury were reduced by inactivation of xanthine oxidase in a rabbit model that simulates the situation of human thoracic aorta operations.

Acid-Base Equilibrium↗

PubMed1993

NMR measurements of Na+ and cellular energy in ischemic rat heart: role of Na(+)-H+ exchange.

Interleaved 23Na- and 31P-nuclear magnetic resonance (NMR) spectra were continuously collected on perfused rat hearts subjected to low-flow ischemia (30 min, 10% flow) or zero-flow ischemia (21 min) followed by reperfusion. During untreated low-flow and zero-flow ischemia, intracellular Na+ (Nai+) increased by 53 +/- 11 (+/- SE) and 78 +/- 8%, respectively, and remained elevated for zero-flow hearts. However, during both low- and zero-flow ischemia, Nai+ did not increase in hearts treated with the Na(+)-H+ exchange inhibitor, 5-(N-ethyl-N-isopropyl)amiloride (EIPA). The pH decreases during ischemia were unchanged. EIPA treatment reduced ATP depletion during ischemia. During reperfusion from zero-flow ischemia, EIPA-treated hearts displayed more rapid and extensive recoveries of phosphocreatine and ATP. Recovery of left ventricular developed pressure was improved for zero-flow hearts treated with EIPA during the ischemic period exclusively (104 +/- 13%) compared with untreated hearts (36 +/- 21%). These data indicate that Na(+)-H+ exchange is an important mechanism for Nai+ accumulation, but not for pH regulation, during myocardial ischemia. Additionally, Nai+ homeostasis plays an important role in the postischemic recovery of cellular energy and ventricular function.

Amiloride↗

PubMed1993

Bence Jones proteins bind to a common peptide segment of Tamm-Horsfall glycoprotein to promote heterotypic aggregation.

Bence Jones proteins (BJPs) are the major pathogenic factor causing cast nephropathy ("myeloma kidney") by coaggregation with Tamm-Horsfall glycoprotein (THP). Understanding the interaction between these proteins is therefore important in developing treatment strategies to prevent renal failure from cast formation in multiple myeloma. We developed an enzyme-linked immunoassay to examine this phenomenon. Five different human BJPs (four kappa and one lambda immunoglobulin light chains) were used in this assay that demonstrated these proteins bound THP with different affinity. BJPs competed among themselves for binding to THP. The binding site was a peptide portion of THP since these proteins also bound deglycosylated THP. Also, one monoclonal antibody directed against a peptide segment of human THP prevented binding of THP to BJPs. By altering the conformation of THP, reducing agents decreased binding between these two proteins in concentration-dependent fashion. In turbidity studies, the monoclonal antibody that prevented binding and a reducing agent, dithiothreitol, decreased coaggregation. Deglycosylated THP did not coaggregate with BJPs. We concluded that ionic interaction between BJPs and a specific peptide binding site on THP promoted heterotypic coaggregation. The carbohydrate moiety of THP was also essential for coaggregation, perhaps by facilitating homotypic aggregation of THP.

Bence Jones Protein↗

PubMed1993

Physiologic levels of uric acid inhibit xanthine oxidase in human plasma.

Xanthine oxidase, a key source of reactive oxygen species, and purine substrates are detected in the circulation after ischemia-reperfusion. High levels of uric acid, produced by a xanthine oxidase-catalyzed reaction, are found in human plasma. We studied whether uric acid could alter xanthine oxidase activity in plasma obtained from eight adults and eight neonates. Known amounts of uric acid were added to xanthine and xanthine oxidase-supplemented buffer and plasma, and the production of uric acid and superoxide was determined. Uric acid, 150 and 300 microM, decreased the oxidation of xanthine to uric acid in adult plasma by 37.5 +/- 5.6 and 48.9 +/- 6.1% and formation of superoxide by 23.2 +/- 1.9 and 32.0 +/- 2.3%, respectively, compared with plasma without uric acid. In newborn plasma, a similar pattern and extent of inhibition was observed. Superoxide formation, however, was inhibited to a greater extent than in adult plasma. Endogenous xanthine oxidase was detected in newborn plasma in nine additional neonates using HPLC. These results indicate that uric acid is an effective inhibitor of the formation of superoxide and hydrogen peroxide by xanthine oxidase at the levels found in human plasma. Plasma uric acid may play an important role in attenuating the oxidant-mediated tissue damage caused by xanthine oxidase released into the circulation during ischemia-reperfusion.

Adult↗

PubMed1993

Hypertensive nephrosclerosis in the Dahl/Rapp rat. Initial sites of injury and effect of dietary L-arginine supplementation.

BACKGROUND: The Dahl/Rapp strains of salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rat were developed to examine pathogenetic mechanisms that produce hypertension in response to an increase in dietary salt. We have shown that providing SS/Jr rats with L-arginine, the metabolic precursor of nitric oxide, acutely prevented salt-sensitive hypertension, suggesting that SS/Jr rats developed hypertension because of inadequate nitric oxide production while on a high-salt diet. EXPERIMENTAL DESIGN: Male 23-day SS/Jr and SR/Jr rats were placed on chow that contained 8% sodium chloride. One group of SS/Jr rats also received L-arginine, 1.25 g/liter, in their drinking water. These three groups were examined at weekly intervals for 4 weeks. RESULTS: SS/Jr rats rapidly developed hypertension when placed on the high-salt chow. After 2 weeks on this diet, inulin clearance dramatically decreased, and albumin excretion rate increased. By the fourth week of study, SS/Jr rats on the high-salt diet had died or were dying. Coincident with the progressive decline in inulin clearance, renal morphologic analysis confirmed development of myointimal thickening, fibrinoid necrosis, and glomerulosclerosis. In contrast, over the 4 weeks of study, SS/Jr rats supplemented with oral L-arginine did not develop hypertension and any of the associated renal complications seen in age-matched SS/Jr rats on the high-salt diet. L-Arginine also corrected hypertension in SS/Jr rats exposed to the high-salt chow for 2 weeks before the inception of L-arginine. L-Arginine administration after 3 weeks on this chow, however, failed to reverse hypertension and the depressed inulin clearance and morphologic renal damage. CONCLUSIONS: Along with previous work (Chen PY, Sanders PW, J Clin Invest 88:1559-67), these studies were consistent with the hypothesis that hypertension and hypertensive nephrosclerosis developed in SS/Jr rats because, while on a high-salt diet, substrate (L-arginine) became a rate-limiting factor in the synthesis of nitric oxide.

Animals↗

PubMed1992

An immunochemical comparison of human myelin basic protein and its modified, citrullinated form, C8.

An immunochemical analysis was conducted to compare the C1 isomer of human myelin basic protein (MBP) with the newly described and less cationic, citrullinated isomer of MBP referred to as C8. Ten polyclonal antisera directed at multiple epitopes or restricted regions of MBP were used in radioimmunoassays to examine MBP-C1 and MBP-C8. Antisera reactive with MBP peptide 1-14 clearly distinguished MBP-C1 from MBP-C8. Antisera to human MBP peptides 10-19 and 90-170, but not to MBP peptide 69-89, showed modest differences between MBP-C1 and MBP-C8. The MBP-C8s from multiple sclerosis (MS) and non-MS brain reacted essentially the same. With murine monoclonal antibodies and enzyme-linked immunosorbent assay (ELISA), differences between MBP-C8 and other isomers were shown for anti-MBP 10-19 but not for anti-MBP 1-9 or anti-MBP 80-89. These findings imply differences in sequence or conformation in the structure of MBP-C7 compared to MBP-C1, most notably near the amino terminus.

Adult↗

PubMed1992

Binding of serum immunoglobulins to collagens in IgA nephropathy and HIV infection.

The mechanism of the binding of IgA to the mesangium in IgA nephropathy (IgAN) is unknown. Interactions between IgA and components of the mesangial matrix may contribute. We measured by enzyme-linked immunosorbent assay the binding of serum IgA, IgG, and IgM from patients with IgAN, human immunodeficiency virus type I (HIV) infection, and healthy controls to purified native collagen types I to VI, and to an extract of normal kidney tissue. HIV infection is an appropriate disease control because of the lack of mesangial IgA deposits, despite high serum levels of IgA and IgA1-containing immune complexes. Increased levels of IgA-binding to collagen types I and V and the kidney extract were found only in IgAN. Both IgAN and HIV-infected patients had increased IgA-binding to collagen types II, III, and VI. Preabsorption of the sera with gelatin substantially reduced the IgA-binding to collagen types I to IV, but not to types V and VI. This finding suggests that the binding to collagen type V is not fibronectin-mediated, but may reflect autoantibody formation. Thus, fibronectin-mediated IgA-collagen interactions are not specific for IgAN, and their pathogenetic role is questionable. The role of IgA anti-collagen type V antibodies requires further study.

Adolescent↗

PubMed1992

Effect of angiotensin converting enzyme inhibitors upon brain angiotensin II binding.

OBJECTIVE: The major objective of the current study was to determine whether administration of converting enzyme (CEI) inhibitors produces an alteration in angiotensin II receptor binding in the spontaneously hypertensive rat (SHR). DESIGN: These studies were designed to test the hypothesis that administration of CEI to SHR is associated with a downregulation of the brain angiotensin II receptor. METHODS: Ten to fifteen rats per group were used as mating pairs to produce the pups used for cell culture. The specific binding of 125I-angiotensin II to cell membranes was determined in primary neuronal enriched cultures (PNC) developed from whole brains of 1-day-old SHR pups treated in utero with captopril compared with control SHR pups. We then determined the effect of short-term incubation of PNC with captopril or lisinopril upon angiotensin II binding kinetics. RESULTS: 125I-angiotensin II binding in PNC from captopril-treated SHR was decreased compared with cells from control rats. Scatchard analysis revealed no differences in receptor affinity but maximum density of binding sites was less in captopril-treated rats than in controls. Short-term incubation of cells with captopril or lisinopril did not affect angiotensin II binding in neuronal cultures from normotensive rats; however, angiotensin II binding was decreased in SHR cells treated with captopril. Angiotensin II binding was also decreased in SHR treated in utero with captopril. CONCLUSIONS: These data suggest that CEI decrease 125I-angiotensin II binding in brains from SHR and, furthermore, that the angiotensin II receptor in SHR may be regulated differently from that of normotensive rats.

Angiotensin II↗

PubMed1992

IgA-containing immune complexes after challenge with food antigens in patients with IgA nephropathy.

The possibility that patients with IgA nephropathy (IgAN) might have abnormal IgA immune responses to immunogens commonly encountered at mucosal surfaces, resulting in the formation of circulating immune complexes (CIC), was examined. Since it is generally held that such increased IgA responses are characterized by detectable aberrancies in handling of IgA-containing CIC, IgAN patients and controls were given a large volume of bovine milk (after dietary deprivation of bovine antigens) and immune complex levels were measured over a period of 12 h. An assay based on binding of CIC containing C3 to solid-phase anti-C3 and subsequent development with isotype-specific antibody revealed no differences in responses of patients and controls with respect to IgG- and IgM-containing CIC. Although IgAN patients tended to have higher levels of IgA-containing CIC, there were no differences in response patterns when IgA CIC levels after ingestion of the milk stimulus were related to baseline levels. Polymorphonuclear leucocytes (PMNC), which bear surface receptors for IgA, were isolated from some subjects at the same times as the samples for CIC levels and examined by two-colour immunofluorescence for the coincident presence of IgA and milk antigens. In contrast to the data obtained in the CIC assays, these experiments revealed the simultaneous presence of IgA and two of three milk proteins in PMNC of IgAN patients but not controls. Follow-up experiments designed to assess more quantitatively the coincidental presence of IgA and milk antigens indicated no significant differences between patients and controls. However, milk proteins seemed to be more commonly associated with IgA in PMNC of IgAN patients, suggesting the presence of non-complement-fixing IgA/antigen CIC after mucosal challenge of some IgAN patients.

Adolescent↗

PubMed1992

Clinical characteristics and outcome of patients with high defibrillation thresholds. A multicenter study.

BACKGROUND: Successful defibrillation by an implantable cardioverter-defibrillator (ICD) depends on its ability to deliver shocks that exceed the defibrillation threshold. This study was designed to identify clinical characteristics that may predict the finding of an elevated defibrillation threshold and to describe the outcome of patients with high defibrillation thresholds. METHODS AND RESULTS: The records of 1,946 patients from 12 centers were screened to identify 90 patients (4.6%) with a defibrillation threshold greater than or equal to 25 J. Excluding three patients who received ICDs that delivered greater than 30 J, there were 81 men and six women with a mean age of 59.5 +/- 10.1 years, a mean left ventricular ejection fraction of 0.32 +/- 0.14, and a 76% prevalence of coronary artery disease. Sixty-one patients (70%) were receiving antiarrhythmic drugs, and 45 (52%) were receiving amiodarone. Seventy-one patients (82%) received an ICD. Death occurred in 27 patients--19 of the 71 (27%) with an ICD (eight arrhythmic), and eight of the 16 (50%) without an ICD (four arrhythmic). Actuarial survival for all patients at 5 years was 67%. Actuarial survival rates at 2 years for patients with and without an ICD were 81% and 36%, respectively (p = 0.0024). Actuarial survival at 5 years for the ICD patients was 73%; no patient without an ICD has lived longer than 32 months. Actuarial survival free of arrhythmic death in the ICD patients at 5 years was 84%. Although the only variable to predict survival was ICD implantation (p = 0.003), it is entirely possible that in this retrospective analysis, clinical selection decisions to implant or to not implant an ICD differentiated patients destined to have better or worse outcomes, respectively. CONCLUSIONS: Antiarrhythmic drug use may be causally related to the finding of an elevated defibrillation threshold. When patients with high defibrillation thresholds receive an ICD, arrhythmic death remains an important risk (42% of deaths in these patients were arrhythmia related, with 16% actuarial incidence at 5 years). Vigorous testing to optimize patch location can potentially benefit patients by enhancing the margin of safety for effective defibrillation.

Adult↗

PubMed1991

Interstudy reproducibility of biplane cine nuclear magnetic resonance measurements of left ventricular function.

Cine nuclear magnetic resonance (NMR) imaging, as a noninvasive and high-resolution imaging modality, has been shown to be reliable for determining absolute left ventricular (LV) volumes and ejection fraction. A relatively new gradient echo cine NMR approach using 2 orthogonal long-axis planes (2- and 4-chamber) aligned with the true axes of the left ventricle has been previously developed and validated against radiographic biplane LV cineangiography. The aim of the present investigation was to determine the reproducibility of this more rapid cine NMR approach for the measurement of LV volumes and ejection fraction. Eighteen normal subjects underwent 2 cine NMR studies, on different days, using a 1.5-tesla clinical imaging system. Studies were analyzed on-line and blindly by 2 independent observers. Intraobserver error was also determined in a blinded manner. Mean values of measurements determined by this method in this group of normal subjects were end-diastolic volume (120 +/- 20 ml), end-systolic volume (39 +/- 9 ml) and ejection fraction (67 +/- 4%). Paired analysis of data revealed no significant bias between interstudy, interobserver or intraobserver measurements, except for interobserver end-diastolic volume, where the first observer measurements were slightly elevated (5.6 +/- 7.8 ml) compared with the second. This resulted in a small difference in ejection fraction (1.7 +/- 2.3%) between observers. The absolute variation between measurements (square root of variance components) was low for all interstudy, interobserver and intraobserver comparisons: end-diastolic volume was less than +/- 6.7 ml, end-systolic volume less than +/- 3.5 ml and ejection fraction less than +/- 2.4%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Selective elevation of monomeric IgA1 in IgA nephropathy patients with normal renal function.

The molecular form of the pathognomonic IgA in IgA nephropathy (IgAN) remains controversial. Because characterization of the molecular form of IgA molecules can lend insight into their origin (systemic v mucosal), we developed immunoassays to measure both total and J chain-containing (polymeric) IgA1 and IgA2. These assays were used to measure IgA in sera from two groups of IgAN patients (with normal or decreased renal function), as well as from a group of normal individuals. IgA1 levels were higher in both groups of patients with IgAN when compared with the controls. The elevation appeared to be restricted to non-J chain-containing (monomeric) IgA1 in patients with normal renal function, whereas polymeric IgA1 was also slightly elevated in patients whose renal function was diminished. While there were no significant differences between the groups in terms of the levels of total IgA2, the patient group with normal kidney function appeared to have lower levels of polymeric IgA2. The observation that the elevation in serum IgA appears to be restricted to the monomeric form of IgA1, at least when renal function is normal, implies a systemic origin of the pathognomonic IgA in IgAN and further suggests an abnormality in the regulation of IgA secretion by immunoglobulin-producing cells in bone marrow, the site of systemic IgA synthesis.

Adolescent↗

PubMed1991

Changing patterns of end-stage renal disease due to hypertension.

We analyzed the records of all residents of Jefferson County, Alabama, accepted for renal replacement therapy between 1982 and 1987 and compared them with those accepted between 1974 and 1978 to determine any changes in the distribution and frequency of end-stage renal disease (ESRD) due to hypertension (H-ESRD). H-ESRD increased from 6.4 to 9.6 per 100,000 in blacks and from 0.36 to 0.62 per 100,000 in whites. Smoothed age- and race-specific yearly H-ESRD rates decreased in blacks under age 50. Peak incidence of H-ESRD shifted from age 40 to 49 in 1974 through 1978 to age 50 to 59 in 1982 through 1987 (P less than 0.0001). Blacks were referred for care with significantly higher blood pressure levels and serum creatinine concentrations than whites, and had more severe retinal vascular disease. Factors significantly associated with a shorter time from referral to renal replacement therapy were black race, female gender, blood urea nitrogen and serum creatinine concentrations, carbohydrate intolerance, and the use of alpha-agonist and/or angiotensin-converting enzyme (ACE) inhibitor. We conclude that racial distribution and risk for H-ESRD have not changed. Peak rates of H-ESRD have been delayed nearly a decade, suggesting a possible effect of better awareness and treatment of hypertension.

Adult↗

PubMed1991

Long-term follow-up of a human subject with a remnant kidney.

It has been proposed that once functioning renal mass has been reduced below a critical level, either as the result of disease, congenital absence of a kidney, or surgical ablation, that hyperfiltration and glomerular hypertension lead to progressive glomerular sclerosis and end-stage renal failure. We report the clinical course and renal function of a human subject followed for 10.8 years after extensive renal ablation. Functioning renal mass was estimated at one fourth to one fifth of normal. During the follow-up period, creatinine clearance increased from 0.27 mL/s (16 mL/min) to 0.88 mL/s (53 mL/min), the total renal plasma flow (all of which was to the left kidney) increased from 62 mL/min to 190 mL/min, and 24-hour urine protein excretion increased from 0.09 g to 0.4 g. Despite probable glomerular hyperfiltration, neither progressive glomerular dysfunction nor end-stage renal failure developed over a period of 10 years.

Adult↗

PubMed1991

Epstein-Barr virus transformation of B lymphocytes from IgA nephropathy patients and first-degree relatives results in increased immunoglobulin synthesis not restricted to IgA.

In order to study B-cell activation patterns independent of T-cell regulation in patients with IgA nephropathy (IgAN), peripheral blood mononuclear cells from 67 patients with IgAN, 15 first-degree relatives of patients with familial disease, and 13 normal controls were transformed with Epstein-Barr virus (EBV). Culture supernatants of these transformed cells were assayed for levels of IgG, IgA, and IgM, and results obtained on the three populations were compared. EBV-transformed cells of IgAN patients, as well as the population of first-degree relatives, secreted significantly elevated levels of all three isotypes as compared with the normal controls. However, in comparing ratios of secreted isotypes, it was determined that more IgA relative to IgG and IgM was synthesized by cells of these two populations as compared with the normal controls. Our results imply that (1) the population of B cells susceptible to EBV activation is increased in IgAN patients; (2) this population of "activatable" B lymphocytes is polyclonal and not restricted to the IgA class; and (3) even though there may be a primary B-cell abnormality in IgAN, an additional defect(s) is probably operative in the pathogenesis, since cells of clinically unaffected relatives behaved in a pattern similar to that of patients.

B-Lymphocytes↗

PubMed1991

Inability of the signal-averaged electrocardiogram to determine risk of arrhythmia recurrence in patients with implantable cardioverter defibrillators.

Signal-averaged electrocardiography has been used to identify patients at risk for arrhythmic death after myocardial infarction. Since patients with implantable cardioverter defibrillators (ICDs) are at high risk for arrhythmic events, they should also be expected to have a high incidence of abnormal signal-averaged electrocardiograms (SAECGs). However, whether the SAECG can discriminate patients who will have arrhythmia recurrence and receive appropriate ICD shocks from those who will have no recurrence and no shocks is unknown. This study examines the usefulness of the SAECG to separate appropriate users from non-users of the ICD. Fifty patients with ICDs participated in this study. Those who received a shock preceded by symptoms, a shock without preceding symptoms but with electrocardiographic documentation of ventricular fibrillation or ventricular tachycardia, or a shock while asleep were classified as ICD users. All other patients were classified as nonusers. The SAECG was classified as normal if the QRS duration on the standard electrocardiogram was less than or equal to 110 msec and if the total filtered QRS duration was less than 120 msec, the root-mean square voltage of the terminal 40 msec was greater than 25 muV, and the terminal low amplitude signal duration measured less than 38 msec. The SAECG was classified as abnormal if the QRS duration on the standard electrocardiogram was less than or equal to 110 msec and any one of these three criteria were outside the "normal range." The SAECG was classified as indeterminate if the QRS duration on the standard 12-lead electrocardiogram was greater than 110 msec. For the entire group of 50 patients, 8 (16%), 12 (24%), and 30 (60%) had normal, abnormal, and indeterminate SAECGs, respectively. Of the 22 ICD users, 1 (5%), 5 (23%), and 16 (73%) patients had normal, abnormal, and indeterminate SAECGs, respectively. Of the 28 ICD nonusers, 7 (25%), 7 (25%), and 14 (50%) patients had normal, abnormal, and indeterminate SAECGs, respectively. ICD users had lower left ventricular ejection fractions (P = 0.0002), a higher incidence of ventricular tachycardia (P = 0.04), prior exposure to a greater number of antiarrhythmic drugs (P = 0.04), and a lower likelihood for survival (P = 0.02) compared to the ICD nonusers. There was no statistically significant difference between the ICD users and nonusers as stratified by SAECG classification regardless of whether or not the interminate studies were included or excluded from the analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Arrhythmias, Cardiac↗

PubMed1991

Carnitine palmitoyltransferase in cardiac ischemia. A potential site for altered fatty acid metabolism.

The sensitivity of carnitine palmitoyl coenzyme A (CoA) transferase I to inhibition of its activity by malonyl-CoA is progressively reduced in mitochondria isolated from ischemic cardiac cells as blood flow decreases to 30% or less of the preocclusion flow. The activity of carnitine palmitoyl-CoA transferase I in mitochondria isolated from nonischemic cardiac cells demonstrates incomplete inhibition, even at high concentrations of malonyl-CoA. Kinetic analyses of these data gave results most consistent with the expression of two overt enzyme activities: one activity that is sensitive to inhibition by malonyl-CoA and one activity that demonstrates little or no sensitivity to such inhibition. The decrease in malonyl-CoA-sensitive activity associated with ischemia results from a 13% decrease in the activity of the sensitive component and a corresponding 13% increase in the activity of the insensitive component. Decreased sensitivity of ischemic carnitine palmitoyl-CoA transferase I to inhibition by malonyl-CoA, together with potential fluctuations in the content of malonyl-CoA in tissue, would increase the synthesis of palmitoylcarnitine during ischemia and facilitate return to the use of fatty acid as a preferred metabolic fuel on reperfusion. This apparent conversion occurs concomitantly with a decrease in the free protein thiol content of the mitochondrial membranes isolated from ischemic cardiac cells. Treatment of the mitochondria from ischemic cardiac cells with dithiothreitol in vitro partially reverses the loss in sensitivity to malonyl-CoA, suggesting the possible role of thiol oxidation in the altered metabolism of ischemic mitochondria. Western blot analysis of these mitochondria using an antibody against carnitine palmitoyltransferase II purified from beef heart demonstrates a 68-kDa protein, which under ischemic conditions apparently is decreased by 2 kDa. These results are more indicative of a modification in protein folding of carnitine palmitoyltransferase than proteolytic changes during ischemia.

Animals↗