Biomedical subjects

R Sciacca

Publications and source records attributed to R Sciacca.

At least 19 recordsLinked to original sources

PubMed2005

APOE-epsilon4 predisposes to cognitive dysfunction following uncomplicated carotid endarterectomy.

BACKGROUND: Between 9% and 23% of patients undergoing otherwise uncomplicated carotid endarterectomy (CEA) develop subtle cognitive decline 1 month postoperatively. The APOE-epsilon4 allele has been associated with worse outcome following stroke. OBJECTIVE: To investigate the ability of APOE-epsilon4 to predict post-CEA neurocognitive dysfunction. METHODS: Seventy-five patients with CEA undergoing elective CEA were prospectively recruited in this nested cohort study and demographic variables were recorded. Patients were evaluated before and 1 month after surgery with a standard battery of five neuropsychological tests. APOE genotyping was performed by restriction fragment length polymorphism analysis in all patients. Neuropsychological deficits were identified by comparing changes (before to 1 month post-operation) in individual performance on the test battery. Logistic regression was performed for APOE-epsilon4 and previously identified risk factors. RESULTS: Twelve of 75 (16%) CEA patients possessed the APOE-epsilon4 allele. Eight of 75 (11%) patients experienced neurocognitive dysfunction on postoperative day 30. One month post-CEA, APOE-epsilon4-positive patients were more likely to be cognitively injured (42%) than APOE-epsilon4-negative patients (5%) (p = 0.002). In multivariate analysis, the presence of the APOE-epsilon4 allele increased the risk of neurocognitive dysfunction at 1 month 62-fold (62.28, 3.15 to 1229, p = 0.007). Diabetes (51.42, 1.94 to 1363, p = 0.02), and obesity (24.43, 1.41 to 422.9, p = 0.03) also predisposed to injury. CONCLUSION: The APOE-epsilon4 allele is a robust independent predictor of neurocognitive decline 1 month following CEA.

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PubMed2004

Thrombin generation in non-cardioembolic stroke subtypes: the Hemostatic System Activation Study.

BACKGROUND: The association between hemostatic activation, stroke mechanism, and outcome is poorly defined. The Hemostatic System Activation Study (HAS) investigators measured serial levels of prothrombin fragment F1.2, a marker of thrombin generation, in patients enrolled in the Warfarin Aspirin Recurrent Stroke Study (WARSS). METHODS: HAS enrolled 631 of the 2,206 patients in WARSS. Strokes were subtyped according to inferred mechanism. Plasma was collected for F1.2 at randomization (within 30 days of stroke), 3 months, 12 months, and 18 months. The 3 to 6 month samples in aspirin-treated patients were used for the primary analysis. RESULTS: The authors analyzed 3 to 6 month samples on 320 patients. Higher F1.2 levels were associated with older age, female sex, and hypertension. There was no difference between mean F1.2 levels in 56 cryptogenic (0.9 +/- 0.32 nmol/L) and 114 non-cryptogenic (1.13 +/- 0.74 nmol/L) patients or across specific stroke subtypes. There was an 8.8%/year (p = 0.006) increase in mean F1.2 levels. There was a trend toward higher risk of recurrent stroke or death as F1.2 levels increased in aspirin (RR: 1.30, 95% CI: 0.57 to 2.94, p = 0.53) and warfarin treated patients (RR: 1.68, 95% CI: 0.48 to 5.94, p = 0.42). F1.2 levels were reduced on average 70% in warfarin-treated patients in a dose-dependent fashion. CONCLUSION: F1.2 levels did not appear to differ by stroke subtype, suggesting that factors other than underlying stroke pathophysiology influence thrombin generation in the post-acute stroke period. F1.2 levels were suppressed by warfarin in a dose-dependent fashion. Additional research is needed to determine the predictive value of F1.2 after stroke.

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PubMed2001

Elevated plasma tissue plasminogen activator and anti-THP-1 antibodies are independently associated with decreased graft survival in cardiac transplant recipients.

Hemostatic and immunologic factors have been implicated in future cardiac events in patients with coronary artery disease. The role of these factors and their interaction is less established in cardiac transplant recipients. We sought to characterize the role of these factors in these patients. Cardiac transplant patients who presented for surveillance coronary angiography and/or endomyocardial biopsy were eligible for enrollment. Ninety-nine consecutive patients were enrolled. Plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1, von Willebrand factor, fibrin D-dimer, and anti-t-PA antibody were determined by enzyme-linked immunosorbent assays. Anti-THP-1 cell antibodies directed against a monocytic leukemia cell line were detected by incubating patient plasma with THP-1 cells. Bound antibody was detected using goat peroxidase-labeled immunoglobulin G directed against human immunoglobulins. Lipids were measured by enzymatic methods. Multivariate analysis identified the presence of anti-THP-1 cell antibodies (risk ratio 4.41, p = 0.002), t-PA antigen (risk ratio 1.10, p = 0.033), donor age 20 to 26 years (risk ratio 8.83, p = 0.042), and donor age >36 years (risk ratio 15.53, p = 0.009) as predictors of allograft failure. Altered hemostatic function, as demonstrated by elevated plasma t-PA antigen levels, is predictive of subsequent allograft failure in cardiac transplant recipients. In addition, the presence of anti-THP-1 cell antibodies in these patients is predictive of allograft failure.

Chi-Square Distribution↗

PubMed2001

Characterization of altered myocardial fatty acid metabolism in patients with inherited cardiomyopathy.

Inherited defects in myocardial long-chain fatty acid metabolism are increasingly recognized as a cause of cardiomyopathy and sudden death in children. To evaluate whether the phenotypic expression of these genetic diseases could be delineated using positron emission tomography (PET), 11 patients with inherited defects in fatty acid metabolism were evaluated and results were compared with those of 6 nonaffected siblings. Myocardial perfusion, myocardial oxygen consumption (MVO2), and long-chain fatty acid metabolism were determined noninvasively with PET using quantitative mathematical models. There were no differences in haemodynamics, perfusion, MVO2 or plasma substrate levels between groups. Patients with defects in enzymes of fatty acid beta-oxidation (acyl-CoA dehydrogenase and 3-hydroxyacyl-CoA dehydrogenase deficiencies) (n = 5) had diminished myocardial palmitate oxidation compared with healthy siblings (3.2 +/- 3.0 vs. 13.0 +/- 5.6 nmol/g per min, p < 0.03) and a decrease in the percentage of MVO2 accounted for by palmitate (2% +/- 3% vs. 9% +/- 5%, p < 0.04). In these patients, extracted palmitate was shunted into a slow-turnover compartment (predominantly reflecting esterification to triglycerides) with expansion of palmitate in that pool (185 +/- 246 compared with 27 +/- 67 nmol/g in healthy siblings,p < 0.02). In contrast, myocardium of patients with carnitine deficiency (n = 6) (all on oral carnitine therapy) had normal palmitate extraction but expansion of the interstitial/cytosolic fatty acid pool (617 +/- 399 vs. 261 +/- 73 nmol/g in healthy siblings, p < 0.04), suggesting different mechanisms for handling upstream fatty acyl intermediates. Thus, PET can be used to noninvasively assess abnormal myocardial handling of fatty acids in patients with inherited defects of metabolism. This approach should be useful in the assessment of altered myocardial fatty acid metabolism associated with cardiomyopathy as well as for evaluating the efficacy of therapeutic interventions in affected patients.

Acetates↗

PubMed2001

Assessment of left ventricular function by real-time 3-dimensional echocardiography compared with conventional noninvasive methods.

Quantitative assessment of left ventricular ejection fraction is an essential component of cardiac evaluation. We performed real-time 3-dimensional echocardiography in 56 consecutive patients who underwent multigated radionuclide angiography. Thirteen patients were excluded for the following reasons: 5 for large size of left ventricle required for image acquisition, 5 for suboptimal image quality in real-time 3-dimensional echocardiography, and 3 for atrial fibrillation. Finally, we compared left ventricular ejection fraction assessed by real-time 3-dimensional echocardiography and conventional 2-dimensional echocardiography with that obtained by multigated radionuclide angiography in 43 patients. Left ventricular ejection fraction was determined by real-time 3-dimensional echocardiography with the use of parallel plane-disks and sector plane-disks summation methods. A good correlation was obtained between both real-time 3-dimensional echocardiography methods and multigated radionuclide angiography (r = 0.87 and 0.90, standard error of estimate = 3.7% and 4.2%), whereas the relation between the 2-dimensional echocardiography method and radionuclide angiography demonstrated a significant departure from the line of identity (P <.001). In addition, interobserver variability was significantly lower (P <.05) for the real-time 3-dimensional echocardiography methods than that by the 2-dimensional echocardiography method. Real-time 3-dimensional echocardiography may be used for quantification of left ventricular function as an alternative to conventional methods in patients with adequate image quality.

Adult↗

PubMed2001

Anesthetic inhibition in ischemic and nonischemic murine heart: comparison with conscious echocardiographic approach.

It is well known that the level of anesthesia obtained by intraperitoneal injection is variable and may alter cardiac function. In this study, we compared the effects of different anesthetics on cardiac function with the conscious state using high-resolution two-dimensional echocardiography in nonischemic and ischemic mice. Eighty-four mice were tested before and after surgery with ligation of the coronary artery. All 84 mice were studied in the conscious state and under high-dose intraperitoneal anesthesia. Twenty-two of 84 mice were studied under low-dose intraperitoneal anesthesia. Another 22 mice were also studied under gas anesthesia and spontaneous breathing. Experiments in the conscious state were performed by two investigators before the administration of anesthesia: one investigator held the animal and the transducer and the other operated the ultrasound equipment. Left ventricular systolic function was measured, and measurements obtained after surgery were compared with infarcted areas assessed by histological staining. Results showed that both high- and low-dose intraperitoneal anesthesia significantly reduced heart rates and left ventricular contractility in both pre- and postsurgical mice as opposed to conscious mice (P < 0.01). There were significantly higher correlation coefficients between mean fractional area change (FAC) and infarcted area in conscious state compared with high-dose intraperitoneal anesthesia (P < 0.05). The correlation coefficient between FAC and infarcted area during gas anesthesia was also significantly higher compared with high-dose intraperitoneal anesthesia (P < 0.05). In conclusion, conscious experiments or the use of gas anesthesia is preferred for echocardiographic assessment of cardiac function in mice because intraperitoneal injection significantly induces a significant reduction in heart rate and left ventricular systolic function.

Anesthetics, Inhalation↗

PubMed2000

Determination of left ventricular mass by real-time three-dimensional echocardiography: in vitro validation.

Twenty-one explanted fixed hearts (14 dogs and 7 pigs) were examined to validate newly developed real-time three-dimensional (RT3D) echocardiography for measurement of left ventricular (LV) mass in vitro and to compare its accuracy and variability with those of conventional echocardiographic measurements. There was an excellent correlation and high degree of agreement for the determination of LV mass between RT3D echocardiography and true mass measurement (r = 0.98; standard error of the estimate [SEE] = 7.3 g; absolute difference [AD] = 2.8 g; y = 1.00 x -4.0, interobserver variability; 5.0%). The conventional echocardiographic methods yielded weaker correlations, larger standard errors, and interobserver variability (area-length method: r = 0.90; SEE = 13.3 g; AD = 13.2 g; 13.3 % / truncated ellipsoid method: r = 0.91; SEE = 14.7 g; AD = 10.5 g; 7. 9% / M-mode: r = 0.91; SEE = 16.2 g; AD = 9.4 g; 15.3%). Determination of LV mass by RT3D echocardiography has a high degree of accuracy and is superior to conventional one- and two-dimensional echocardiographic methods.

Animals↗

PubMed2000

Acute elevations of plasma asymmetric dimethylarginine and impaired endothelial function in response to a high-fat meal in patients with type 2 diabetes.

Asymmetric dimethylarginine (ADMA), a compound detectable in human plasma, is an endogenous inhibitor of NO synthase. Endothelial dysfunction is an early event in atherogenesis, and large-vessel atherosclerosis is a major cause of morbidity and mortality in patients with type 2 diabetes mellitus. Fifty patients with type 2 diabetes mellitus were studied at baseline and 5 hours after ingestion of a high-fat meal. Plasma ADMA measured by using high-performance liquid chromatography increased from 1.04+/-0.99 to 2.51+/-2.27 micromol/L (P:<0.0005). Brachial arterial vasodilation after reactive hyperemia, a NO-dependent function, measured by high-resolution ultrasound, decreased from 6.9+/-3.9% at baseline to 1.3+/-4.5% (P:<0.0001). These changes occurred in association with increased plasma levels of triglycerides and very low density lipoprotein triglycerides, with reduced low density lipoprotein cholesterol and high density lipoprotein cholesterol, and with no changes in total cholesterol. The increase in plasma ADMA in response to a high-fat meal was significantly and inversely related to the decrease in percent vasodilation. In 10 of the subjects studied with a similar protocol on another day, no significant changes in the brachial artery flow responses or in plasma ADMA were observed 5 hours after ingestion of a nonfat isocaloric meal. The data suggest that ADMA may contribute to abnormal blood flow responses and to atherogenesis in type 2 diabetics.

Adult↗

PubMed1999

New-onset sustained ventricular tachycardia after cardiac surgery.

BACKGROUND: The de novo occurrence of sustained ventricular tachycardia (VT) after CABG has been described, but the incidence, mortality rate, long-term follow-up, and mechanism are not well defined. METHODS AND RESULTS: This prospective study enrolled consecutive patients undergoing CABG at a single institution. Patients were followed up for the development of sustained VT, and a detailed analysis of clinical, angiographic, and surgical variables associated with the occurrence of VT was performed. A total of 382 patients participated, and 12 patients (3.1%) experienced >/=1 episode of sustained VT 4.1+/-4.8 days after CABG. In 11 of 12 patients, no postoperative complication explained the VT; 1 patient had a perioperative myocardial infarction. The in-hospital mortality rate was 25%. Patients with VT were more likely to have prior myocardial infarction (92% versus 50%, P<0.01), severe congestive heart failure (56% versus 21%, P<0.01), and ejection fraction <0.40 (70% versus 29%, P<0.01). When all 3 factors were present, the risk of VT was 30%, a 14-fold increase. Patients with VT had more noncollateralized totally occluded vessels on angiogram (1.4+/-0.97 versus 0.54+/-0.7, P<0.01), a bypass graft across a noncollateralized occluded vessel (1.50+/-1.0 versus 0.42+/-0.62, P<0.01), and a bypass graft across a noncollateralized occluded vessel to an infarct zone (1.50+/-1.0 versus 0.17+/-0.38, P<0.01). By multivariate analysis, the number of bypass grafts across a noncollateralized occluded vessel to an infarct zone was the only independent factor predicting VT. CONCLUSIONS: The first presentation of sustained monomorphic VT in the recovery period after CABG is uncommon, but the incidence is high in specific clinical subsets. Placement of a bypass graft across a noncollateralized total occlusion in a vessel supplying an infarct zone was strongly and independently associated with the development of VT.

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PubMed1998

Reversal of iatrogenic myocardial edema and related abnormalities of diastolic properties in the pig left ventricle.

OBJECTIVE: This study examines the resolution of iatrogenic edema and related changes in systolic and diastolic properties in the intact pig left ventricle. METHODS: The coronary arteries were perfused for 50 to 60 seconds with diluted blood (hematocrit value 10% +/- 1%, edema group, n = 5) or whole blood (hematocrit value 28% +/- 1%, control group, n = 6) infused into the aortic root during aortic crossclamping in conditioned, anesthetized pigs. After whole blood reperfusion, preload reduction by vena caval occlusion was used to define systolic and diastolic properties at 15-minute intervals. Left ventricular pressure and conductance, aortic flow, and two-dimensional echocardiography were recorded. RESULTS: Left ventricular mass (wall volume) in the edema group increased significantly compared with that in control pigs after crossclamp removal. Mass returned to preperfusion levels after 45 minutes. The ventricular stiffness constant (beta) increased significantly in the edema group versus the control group, returning to baseline by 30 minutes. The diastolic relaxation constant (tau) and base constant (alpha) did not differ between groups. There was no significant change in contractility. CONCLUSION: Increases in left ventricular mass and diastolic stiffness induced by coronary perfusion with hemodiluted blood resolve after 45 minutes of whole blood perfusion in pigs. This study defines physiologic effects of edema in the normal heart while eliminating most common confounding experimental errors.

Animals↗

PubMed1998

A method for detecting changes in left ventricular mass during variations in filling volume.

Two-dimensional echocardiography has been useful for measuring changes in left ventricular mass (LVM) at constant left ventricular end-diastolic volume (LVEDV). Two-dimensional echocardiographic measurement of LVM changes during variations in LVEDV requires definition of the LVM/LVEDV relation because two-dimensional echocardiographic measurements could be affected by asymmetrical redistribution of LVM. Echocardiography data were recorded during caval occlusions in pigs (n = 6). Results confirm that A(M) (left ventricular [LV] short-axis cross-sectional [SACS] wall thickness area), was inversely related to AL (LV SACS lumen area), the average relation being A(M) = -0.33 AL + 20 (r = 0.82 +/- 0.05 [SE]). In addition, we developed a model that computes normal relation between LV SACS wall thickness area (AMc) and LV SACS lumen area (ALc) over a physiologic range of LVEDVs based on a single end-diastolic two-dimensional echocardiographic SACS image. Each computed relation corresponds uniquely to an LVM (LVMc). Theoretically, a difference between AMc/ALc relation before an intervention and the computed relation after the intervention would indicate a change in LVM. To test the utility of this model, edema was induced in a second group of pigs (n = 6) by coronary hemodilution. Two conditions were tested: pre-edema and edema. Serial AMc/ALc and LVMc were computed. Pre-edema and edema AMc were compared at matched LV SACS end-diastolic areas (ALc = 15 cm2). Results showed a significant increase in LVMc (two-tailed p value < 0.05), as observed by two-dimensional echocardiography. We conclude that the A(M) and AL are inversely related. This relation is useful for detecting alterations in LVM during variations in LVEDV.

Animals↗

PubMed1998

Effect of improved myocardial protection on edema and diastolic properties of the rat left ventricle during acute allograft rejection.

BACKGROUND: Studies of myocardial edema and diastolic dysfunction in rat heart transplantation have been flawed by ischemic injury. This study uses improved methods to prevent ischemic contracture. METHODS: Hearts of 30 ACI rats were transplanted into the abdomen of Lewis rats by use of cold University of Wisconsin solution for improved preservation. Left ventricular diastolic properties were expressed as volume at standardized pressure intervals. RESULTS: On posttransplantation day 3, mean left ventricular volume at 15 mm Hg in allografts (290 +/- 9 microl, SEM) was not significantly different vs isografts (299 +/- 32 microl), allografts on day 0 (337 +/- 28 ml) or day 1 (324 +/- 20 microl), or native hearts (334 +/- 19 microl). However, volume was reduced to 173 +/- 17 microl on day 4 and to 70 +/- 23 microl on day 5 (p < 0.05). Similar findings were obtained for volume at 5 and 10 mm Hg. Allograft myocardial water content on day 3, 76.3% +/- 5%, similar to allografts on day 0 and 1 and to isografts on day 3, increased to 77.6% +/- 8% on day 4 (NS) and 79.4% +/- 6% on day 5 (p < 0.05 vs day 0). Histologically, rejection in allografts was mild on day 3, moderate on day 4, and severe on day 5. CONCLUSIONS: Reduced left ventricular filling volume during rejection is only partially explained by edema. Abnormalities of diastolic properties previously attributed to the unloaded state of nonworking heart models may actually reflect inadequate peritransplantation myocardial protection.

Adenosine↗

PubMed1997

Plasma levels of tissue plasminogen activator and plasminogen activator inhibitor-1 are correlated with the presence of transplant coronary artery disease in cardiac transplant recipients.

Hemostatic factors are involved in the pathogenesis of native coronary artery disease. However, their role in transplant coronary artery disease is less established. To assess the role of hemostatic factors in transplant coronary artery disease we studied 52 consecutive cardiac transplant patients. The presence of transplant coronary artery disease was determined by angiography. Plasma levels of tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von Willebrand Factor (vWF), and fibrin D-dimer were determined by enzyme-linked immunosorbent assays. Serum lipids were measured by enzymatic methods. Patients with transplant coronary artery disease had higher circulating t-PA (8.6 +/- 0.8 vs. 5.4 +/- 0.6 ng/ml, p = 0.021) and PAI-1 antigen concentrations (38.0 +/- 3.4 vs 25.8 +/- 2.2 ng/ml, p = 0.037). t-PA and PAI-1 antigen concentrations correlated with the severity of angiographic disease (R = 0.34; p = 0.014 for t-PA, and R = 0.45; p = 0.001 for PAI-1). Serum cholesterol levels were higher in patients with transplant coronary artery disease (221 +/- 7.6 vs 191 +/- 9.2 mg/dl, p = 0.039). Serum triglycerides were also higher in patients with transplant coronary artery disease by angiography (246 +/- 38.3 vs 139 +/- 20.8 mg/dl, p = 0.050). Multivariate analysis identified t-PA antigen (p = 0.003) and triglyceride levels (p = 0.038) as independent predictors for the presence of transplant coronary artery disease. We conclude that cardiac transplant patients with evidence of transplant coronary artery disease on coronary angiography have altered hemostatic function which is reflected by elevated levels of circulating t-PA and PAI-1 antigens. The interaction of the hemostatic system and serum lipids in the development of transplant coronary artery disease warrants further study.

Cholesterol↗

PubMed1995

Psychosocial evaluation and prediction of compliance problems and morbidity after heart transplantation.

We examined prospectively determined psychosocial evaluation data in 125 consecutive adult patients undergoing heart transplantation from January 1992 to April 1994 to determine their associations with morbidity, mortality, and compliance. Prospective ratings included age, sex, weight, education, social support, living arrangements, motivation, knowledge and expectations about transplantation, intercurrent social stressors, substance abuse, personality disorder, cognitive impairment, other psychiatric disorders, and the evaluating psychiatrist's global assessment of psychosocial risk. Additional variables evaluated were support group attendance and waiting list time. We examined outcomes including patient survival, compliance, episodes of rejection and infection, development of transplant coronary artery disease, number of missed appointments, and maintenance of ideal body weight. The posttransplant follow-up period was 13.8 +/- 9.9 months (mean +/- SD). In univariate analyses, compliance problems were associated with substance abuse history (P = .0007), personality disorder (P = .007), living arrangements (P = .02), and global psychosocial risk (P = .001). The number of rejection episodes was associated with global psychosocial risk (P = .029), and transplant coronary artery disease was inversely associated with education (P = .01). Survival was not associated with any of the predictor variables. In stepwise multivariate analyses, the significant predictors of compliance were substance abuse (odds ratio 3.69, confidence limits 1.07-12.71) and global psychosocial risk (odds ratio 3.76, confidence intervals 1.18-11.97). These findings suggest that pretransplant evaluation of psychosocial risk factors can identify patients with increased risk of postoperative noncompliance and morbidity.

Adult↗

PubMed1995

Effects of immunosuppressive therapy on expression of inducible nitric oxide synthase (iNOS) during cardiac allograft rejection.

Recent studies have indicated a role for nitric oxide (NO) in alloimmune responses and in allograft rejection. iNOS mRNA, protein and enzyme activity are induced in myocardium during cardiac allograft rejection. NO produced by iNOS is negatively inotropic and has the potential to be cytotoxic to cardiac myocytes. To investigate whether immunosuppressive agents would alter the expression of iNOS during cardiac allograft rejection, hearts from Wistar-Furth rats were transplanted into the abdomen of Lewis recipients. At day 5 allografts from treated and untreated animals were removed for pathological and biochemical examination. At day 5 the untreated allografts exhibited histological evidence of marked rejection (edema, infiltration with macrophages and lymphocytes, necrosis of cardiac muscle fibers). Abundant iNOS mRNA was apparent in Northern blots and iNOS enzyme activity was increased in ventricular homogenates and in cardiac myocytes purified from the untreated rejecting allografts. Incubation of isolated purified cardiac myocytes from normal rats for 24 h with cytokines known to be present during allograft rejection (IL-1 beta, TNF-alpha and IFN-gamma) was also associated with increased iNOS mRNA and enzyme activity. When Wistar-Furth to Lewis allografts were treated from time of transplantation with FK 506, cyclosporine A, dexamethasone or a combination of all three drugs, histological evidence of rejection and the levels of iNOS mRNA and enzyme activity in ventricular homogenates were reduced significantly below those observed in the untreated allografts. The data in a rat model indicate that immunosuppressive drugs reduce myocardial iNOS mRNA and enzyme activity in rejecting cardiac allografts. The results are consistent with the hypothesis that the alloimmune response and cytokine release are involved in the expression of iNOS during cardiac transplantation rejection.

Animals↗

PubMed1994

Moricizine concentration to guide arrhythmia treatment: with attention to elderly patients.

To test the relationship between plasma moricizine concentration and the electrocardiogram (ECG) and arrhythmia suppression, 17 symptomatic cardiac patients with 30 or more ventricular premature complexes per hour were studied. Seven patients were mature adults, less than 60 years of age; and ten were elderly adults, more than 60 years of age. During steady-state moricizine therapy, patients had plasma moricizine concentration determined over a dosing interval, and had standard 12-lead ECG and a 24-hour ambulatory ECG recorded. The mean moricizine dose was 215 +/- 29 mg every 8 hours; mean maximal moricizine concentration was 1.4 +/- 0.84 micrograms/ml; and mean t1/2 beta was 1.5 +/- 0.7 hours. Baseline age-related differences were found, including prolonged electrocardiographic intervals (PR and QRS) (P < .05), increased ventricular arrhythmias (P < .05), and reduction in creatinine clearance (P < .05) in the elderly. Compared with pretreatment values, PR (P < .05) and QRS (P < .05) prolongation was observed, and was more marked in elderly patients. Over a dosing interval, there were dynamic changes on the ECG that paralleled plasma moricizine concentration; that is, peak and nadir intact moricizine concentration occurred simultaneously with ECG changes: QRS and JTc prolonged (P < .05), and PR prolongation approached significance (P = 0.09). Suppression of ventricular premature complexes of 80% or more occurred in 15 patients, and ventricular tachycardia was abolished in 10 of 12 patients. Probit analysis revealed that the therapeutic antiarrhythmic concentration ranged from 0.20 to 3.6 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Diastolic function in the heterotopic rat heart transplant model. Effects of edema, ischemia, and rejection.

Decreased systolic ventricular function and compliance and increased left ventricular edema and mass have been demonstrated in cardiac allograft rejection. Whether decreased left ventricular compliance in rejection is caused by myocardial edema has not been examined, and compliance in the Ono-Lindsey model has not been reported. Heterotopic rat abdominal cardiac transplantation was performed in ACI isografts (n = 24) and in ACI to Lewis allografts (n = 24). Subgroups were studied on posttransplantation days 0, 1, 3, and 5 (each n = 6). Both transplanted hearts and native hearts were arrested with potassium for the assessment of myocardial water content, heart weight, and the left ventricular pressure-volume relation. In transplanted hearts, myocardial water content did not change in isografts but increased on posttransplantation day 5 in allografts (81.1% on posttransplantation day 5 versus 76.1% on day 0, 77.2% on day 1, and 77.5% on day 3, p < 0.05). Wet and dry heart weight also increased on posttransplantation day 5 in allografts (p < 0.05). The left ventricular pressure-volume relation in transplanted hearts shifted to the left when compared with that in native hearts in all subgroups; these volume differences were statistically significant (p < 0.01) for all pressures above 7.5 mm Hg. This pattern was similar in isografts and allografts on posttransplantation days 0, 1, and 3, and no significant differences between isografts and allografts were demonstrated. On posttransplantation day 5, however, the pressure after a 0.05 ml injection in allografts was greater in transplanted hearts than in native hearts (24 +/- 3 versus 3 +/- 1 mm Hg, p < 0.01). The pressure difference between transplanted and native hearts was also significantly greater in allografts than in isografts (22 +/- 2 versus 6 +/- 1 mm Hg, p < 0.01), indicating an increase in stiffness of allografts. Thus edema and impaired diastolic properties occur concurrently with allograft rejection. Left ventricular volume is abnormal from posttransplantation days 0 to 5 in transplanted hearts but not native hearts in the Ono-Lindsey model with current methods, apparently because of ischemic injury during transplantation.

Animals↗

PubMed1993

Value of the P-wave signal-averaged ECG for predicting atrial fibrillation after cardiac surgery.

BACKGROUND: Atrial fibrillation (AF) is a commonly encountered arrhythmia in clinical practice, and it occurs frequently after cardiac surgery. The P-wave signal-averaged (SA) ECG noninvasively detects atrial conduction delay. Prior studies have described greater P-wave prolongation in patients with a history of AF, but prospective studies have not been performed. METHODS AND RESULTS: Consecutive patients undergoing cardiac surgery were enrolled. The P-wave SAECG was recorded before surgery from three orthogonal leads using a sinus P-wave template and a cross-correlation function. The averaged P wave was filtered with a least-squares-fit filter and combined into a vector magnitude, and total P-wave duration was measured. Patients were observed after cardiac surgery for the development of AF. One hundred thirty patients were enrolled, and 33 (25%) developed AF 2.6 +/- 2.0 days after surgery. Patients with AF more often had left ventricular hypertrophy on ECG (P < .05) and had a lower ejection fraction (P < .05). The P-wave duration on the SAECG was significantly longer in the AF patients than in those without AF: 152 +/- 18 versus 139 +/- 17 milliseconds (P < .001). An SAECG P-wave duration > 140 milliseconds predicted AF with sensitivity of 77%, specificity of 55%, positive predictive accuracy of 37%, and negative predictive accuracy of 87%. The likelihood of experiencing AF was increased 3.9-fold if the SAECG P-wave duration was prolonged. P-wave SAECG results were independent of other clinical variables by multivariate analysis. CONCLUSIONS: The P-wave duration recorded with the SAECG is a potent, accurate, and independent predictor of AF after cardiac surgery.

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