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Biomedical subjects

M F Newman

Publications and source records attributed to M F Newman.

At least 37 records · Page 2Linked to original sources
PubMed2001

Neurological injury during cardiopulmonary bypass in the rat.

Cerebral injury is a well-known complication of cardiac surgery. Investigations of both injury mechanisms and neuroprotective strategies have partially been limited by the lack of an adequate preclinical model of small animal cardiopulmonary bypass (CPB). We sought to determine if neurological injury could be demonstrated in a recovery model of complete CPB in the rat. Rats (n = 5) underwent 45 min of normothermic CPB followed by 24 h of recovery. Compared to sham-operated rats (n = 5), the CPB group showed a worse neurological outcome score (median, 25-75th percentile) compared to controls (5, 4-7 vs 9, 8-9, p = 0.016). This rat model of CPB may allow for the study of CPB-associated neurological injury.

Animals↗
PubMed2000

Beta(2)-adrenergic and several other G protein-coupled receptors in human atrial membranes activate both G(s) and G(i).

Cardiac G protein-coupled receptors that couple to Galpha(s) and stimulate cAMP formation (eg, beta-adrenergic, histamine, serotonin, and glucagon receptors) play a key role in cardiac inotropy. Recent studies in rodent cardiac myocytes and transfected cells have revealed that one of these receptors, the beta(2)-adrenergic receptor (AR), also couples to the inhibitory G protein Galpha(i) (activation of which inhibits cAMP formation). If beta(2)ARs could be shown to couple to Galpha(i) in the human heart, it would have important ramifications, because levels of Galpha(i) increase with age and in failing human heart. Therefore, we investigated whether beta(2)ARs in the human heart activate Galpha(i). By photoaffinity labeling human atrial membranes with [(32)P]azidoanilido-GTP, followed by immunoprecipitation with antibodies specific for Galpha(i), we found that Galpha(i) is activated by stimulation of beta(2)ARs but not of beta(1)ARs. In addition, we found that other Galpha(s)-coupled receptors also couple to Galpha(i), including histamine, serotonin, and glucagon. When coupling of these receptors to Galpha(i) is disrupted by pertussis toxin, their ability to stimulate adenylyl cyclase is enhanced. These data provide the first evidence that beta(2)AR and many other Galpha(s)-coupled receptors in human atrium also couple to Galpha(i) and that abolishing the coupling of these receptors to Galpha(i) increases the receptor-mediated adenylyl cyclase activity.

Adenylate Cyclase Toxin↗
PubMed2000

Intraoperative physiologic variables and outcome in cardiac surgery: Part I. In-hospital mortality.

BACKGROUND: Risk stratification schemes have been developed to predict outcome of coronary artery bypass grafting (CABG) procedures, which are predominately based upon unalterable preoperative patient characteristics. The purpose of this study was to determine if minimum intraoperative hematocrit, maximum glucose concentration, mean arterial pressure on cardiopulmonary bypass, or duration of bypass influence risk-adjusted in-hospital mortality after CABG. METHODS: Outcome data from 2,862 CABG patients were merged with intraoperative physiologic data. A preoperative mortality risk index was calculated for each patient. Variables found significant (p<0.05) by univariate logistic regression were tested in a multiple variable model to determine risk-adjusted association with mortality. RESULTS: Overall mortality rate was 1.85%. The preoperative risk index was significantly associated with mortality (p = 0.0001). No significant association was present between mortality and intraoperative variables. Preexisting hypertension was an independent predictor of mortality after controlling for risk index and bypass duration. CONCLUSIONS: Preexisting hypertension proved to be an independent predictor of mortality in our patient population. This study found no evidence to support the hypothesis that mean arterial pressure less than 50 mm Hg, lower hematocrit, or elevated glucose while on bypass increases in-hospital mortality.

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PubMed2000

Intraoperative physiologic variables and outcome in cardiac surgery: Part II. Neurologic outcome.

BACKGROUND: The impact of alterable physiologic variables on neurologic outcome after coronary artery bypass grafting procedures is unknown. The purpose of this study was to determine whether minimum intraoperative hematocrit, maximum glucose concentration, or mean arterial pressure during cardiopulmonary bypass influences risk-adjusted neurologic outcome after coronary artery bypass grafting. METHODS: Outcome data from 2,862 patients undergoing coronary artery bypass grafting were merged with intraoperative physiologic data. A preoperative stroke risk index was calculated for each patient. Variables found significant by univariate logistic regression were tested in a multivariable model to determine association with outcome. RESULTS: The incidence of stroke or coma in the study population was 1.3%. After controlling for stroke risk and bypass time, only an index of low mean arterial pressure during bypass retained a significant inverse association with outcome (p = 0.0304). CONCLUSIONS: This study found no evidence that glucose concentration or minimum hematocrit are associated with major adverse neurologic outcome. The association between lower pressure during bypass and decreased incidence of stroke or coma persisted in all risk groups. This points to mechanisms other than hypoperfusion as the primary cause of neurologic injury associated with cardiac surgery.

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PubMed2000

Central nervous system complications of cardiac surgery.

The neurological complications of cardiac surgery are associated with significantly increased mortality, morbidity and resource utilization. The use of new surgical techniques, introduction of wider indications for surgery and increased public expectation has led to an increase in the average age of cardiac surgical patients and an increased incidence of repeat procedures. With these changes has come an increased risk of neurological complications. The likelihood of perioperative stroke varies between 1% and 5% in most published series and is dependent on a multitude of risk factors. Of these, patient age, aortic atheroma, symptomatic cerebrovascular disease, diabetes mellitus and the type of surgery appear to be most important. Cognitive deterioration after cardiac surgery is far more common, affecting as many as 80% of patients a few days after surgery and persisting in one-third. Despite an increase in the age of the cardiac surgical population, the reported incidence of cognitive dysfunction after cardiac surgery seems to have fallen in recent years. Whether this is a real phenomenon or the result of changes in the use of psychometric testing and the definition of cognitive decline remains unclear. Recognition that certain equipment, surgical practices and patient factors contribute to neurological morbidity has prompted 'neuroprotective' interventions. Some of these (e.g. arterial line filtration and alpha-stat management) have been shown to improve outcome. Despite these measures, a small number of patients will inevitably sustain cerebral injury during otherwise successful cardiac surgery. Although pharmacological neuroprotection may, in the future, offer some of these patients an improved outcome, it is unlikely that any single agent will prevent neurological injury. In the meantime, the CNS complications of cardiac surgery remain a fertile area of research.

Biomarkers↗
PubMed2000

Off-pump versus on-pump coronary artery bypass surgery and postoperative renal dysfunction.

UNLABELLED: Renal dysfunction is a serious complication after coronary bypass surgery with cardiopulmonary bypass (CABG). Because duration of cardiopulmonary bypass (CPB) is associated with renal outcome, it has been proposed that avoidance of CPB with off-pump coronary bypass (OPCAB) may reduce perioperative renal insult. We therefore tested the hypothesis that OPCAB is associated with less postoperative renal dysfunction compared with CABG surgery. With IRB approval, we gathered data for 690 primary elective coronary bypass patients (OPCAB, 55; CABG, 635). Perioperative change in creatinine clearance (DCrCl) was calculated by using preoperative (CrPre) and peak postoperative (CrPost) serum creatinine values, and the Cockroft-Gault equation (DCrCl = CrPreCl - CrPostCl). Univariate and linear multivariate tests were used in this retrospective analysis; P: < 0.05 was considered significant. Multivariate analysis did not identify OPCAB surgery as an independent predictor of DCrCl. However, previously reported associations of PreCrCl, age, and diabetes with DCrCl were confirmed. Power analysis demonstrated an 80% power to detect a 7.0 mL/min DCrCl difference between study groups. In this retrospective study, we could not confirm that OPCAB significantly reduces perioperative renal dysfunction compared with CABG surgery. Our findings suggest that reduction of renal risk alone should not be an indication for OPCAB over CABG surgery. IMPLICATIONS: Retrospective analysis did not identify any significant difference in perioperative change in creatinine clearance after coronary revascularization with cardiopulmonary bypass compared with off-pump coronary surgery.

Biomarkers↗
PubMed2000

The association of epsilon-aminocaproic acid with postoperative decrease in creatinine clearance in 1502 coronary bypass patients.

UNLABELLED: Renal dysfunction is a common serious complication after cardiac surgery. Reports of proteinuria and hyperkalemia after cardiac surgery with epsilon-aminocaproic acid (EACA) have therefore raised concerns for renal safety. Since EACA renders these markers unreliable, we used perioperative change in creatinine clearance (DCrCl) to test the hypothesis that EACA is associated with greater reductions in creatinine clearance after heart surgery, particularly for patients with renal disease. We evaluated data from all elective primary coronary bypass patients during EACA introduction at our institution (July 1, 1991-December 31, 1992; 10 g iv bolus pre-cardiopulmonary bypass, then 1 g/h for 5 h). DCrCl was calculated using preoperative (CrPre) and postoperative peak serum creatinine values, using the Cockroft-Gault equation. Patients with CrPre > or = 133 micromol/L were also separately analyzed. Evaluated patients (n = 1502, +/-EACA; 581/905, 16 exclusions) included 233 with CrPre > or = 133 micromol/L (+/-EACA; 98/135). Multivariate analyses confirmed several known risk factors, but no association between DCrCl and EACA in all patients (P: = 0.66), and the subgroup with CrPre > or = 133 micromol/L (P: = 0.42). IMPLICATIONS: In a large population of primary Coronary Artery Bypass Graft including a subset with preoperative renal dysfunction, there were no postoperative reductions in creatinine clearance attributable to epsilon-aminocaproic (EACA) administration. This retrospective study suggests that moderate epsilon-aminocaproic acid dosing during cardiac surgery is safe for the kidney; however, this inference is based on a single marker of renal dysfunction and requires prospective confirmation using a variety of tests of renal function.

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PubMed2000

Preliminary report on the association of apolipoprotein E polymorphisms, with postoperative peak serum creatinine concentrations in cardiac surgical patients.

BACKGROUND: Renal dysfunction after cardiac surgery occurs in up to 8% of patients and is associated with major increases in morbidity, mortality, and cost. Genetic polymorphisms have been implicated as a factor in the progression of chronic renal disease, but a genetic basis for the development of acute renal impairment has not been investigated. The authors therefore tested the hypothesis that apolipoprotein E alleles are associated with different postoperative changes in serum creatinine after cardiac surgery. METHODS: The authors performed a prospective observational study with use of data from 564 coronary bypass surgical patients who were enrolled in an ongoing investigation of apolipoprotein E genotypes and organ dysfunction at a university hospital between 1989-1999. Renal function was assessed among apolipoprotein E genotype groups by comparisons of preoperative (CrPre), peak in-hospital postoperative (CrMax) and perioperative change (DCr) in serum creatinine values. RESULTS: The epsilon4 allele grouping (E2 = 2/2,2/3,2/4; E3 = 3/3; E4 = 3/4,4/4) was associated with a smaller increase in postoperative serum creatinine (perioperative change: E4, +0.17; E3, +0.26; E4, +0.27 mg/dl) and a lower peak postoperative creatinine than the epsilon2 and epsilon3 in univariate and multivariate analysis (peak in-hospital postoperative serum creatinine multivariate P = 0.015 vs. epsilon3, P = 0.038 vs. epsilon2). There was no difference in baseline creatinine among allele groups. CONCLUSIONS: Inheritance of the apolipoprotein epsilon4 allele is associated with reduced postoperative increase in serum creatinine after cardiac surgery, compared with the epsilon3 or epsilon2 allele. This is the first report of a possible genetic basis for acute renal impairment. These data may contribute to renal risk stratification for cardiac surgery and raise questions regarding apolipoprotein E and the pathophysiology of acute renal injury.

Acute Disease↗
PubMed1999

Epsilon-aminocaproic acid administration and stroke following coronary artery bypass graft surgery.

BACKGROUND: Epsilon-aminocaproic acid is routinely used to reduce bleeding during cardiac surgery. Anecdotal reports of thrombotic complications have led to speculation regarding this drug's safety. We investigated the association between epsilon-aminocaproic acid administration and postoperative stroke. METHODS: Six thousand two hundred ninety-eight patients undergoing isolated coronary artery bypass graft surgery between 1989 and 1995 were studied. Data was obtained from the Duke Cardiovascular Database as well as from an automated intraoperative anesthesia record keeper. Patients identified as having postoperative stroke were reviewed and confirmed by a board certified neurologist blinded to epsilon-aminocaproic acid administration. RESULTS: Postoperative stroke occurred in 97 patients (1.5%). Three thousand one hundred thirty-five (49.8%) patients received epsilon-aminocaproic acid. Increased age was associated with a higher incidence of postoperative stroke (p = 0.0001). In contrast, there was no significant difference (p = 0.7370) in the incidence of stroke between use of epsilon-aminocaproic acid (1.3%) and nonuse (1.7%). Multivariable logistic regression found no significant effect of epsilon-aminocaproic acid use on stroke after accounting for age, date of surgery, and history of diabetes. CONCLUSIONS: This series suggests that epsilon-aminocaproic acid administration does not increase the risk of postoperative stroke.

Adult↗
PubMed1999

Cognitive decline after major noncardiac operations: a preliminary prospective study.

BACKGROUND: Cardiac operations frequently are complicated by postoperative cognitive decline. Less common and less studied is postoperative cognitive decline after noncardiac surgery, so we determined its incidence, severity, and possible predictors. METHODS: Twenty-nine patients who had thoracic and vascular procedures were studied. A neurocognitive test battery was administered preoperatively and 6 to 12 weeks postoperatively. A change score (preoperative minus postoperative) was calculated for each measure in each individual. Cognitive deficit (a measure of incidence) was defined as a 20% decrement in 20% or more of the completed tests. The average scores of all tests and the average decline (a measure of severity) were determined. RESULTS: The incidence of cognitive deficit was 44.8%. Overall the severity of the decline was an average of 15% decline. In the 44.8% of patients who had cognitive deficit, the severity was 24.7%. Multivariable predictors of cognitive decline were age (for incidence and severity) and years of education (for severity). CONCLUSIONS: Cognitive decline after noncardiac operations is a frequent complication of surgical procedures. The severity could preclude successful return to a preoperative lifestyle.

Adult↗
PubMed1999

Acute renal failure following cardiac surgery.

BACKGROUND: Acute renal failure requiring dialysis (ARF-D) occurs in 1.5% of patients following cardiac surgery, and remains a cause of major morbidity and mortality. While some preoperative risk factors have been characterized, the influence of preoperative and intraoperative factors on the occurrence of ARF following cardiac surgery is less well understood. METHODS: Preoperative and intraoperative data on 2843 consecutive adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) from February 1, 1995 to February 1, 1997 were recorded and entered into a computerized database. Two definitions of renal failure were employed: (i) ARF defined as a rise in serum creatinine (Cr) of 1 mg/dl above baseline; and (ii) ARF-D defined as the development of ARF for which some form of dialytic therapy was required. The association between preoperative and intraoperative variables and the development of ARF was assessed by multivariate logistic regression. RESULTS: A total of 2672 of the 2844 patients underwent isolated coronary artery bypass grafting (CABG) surgery, the remaining 172 underwent valve surgery with or without bypass grafting. Of the CABG patients 7.9% developed ARF and 0.7% developed ARF-D. The mortality for patients who developed ARF was 14% (OR 15, P = 0.0001) compared with 1% among those who did not develop ARF. The mortality for CABG patients who developed ARF-D was 28% (OR 20, P = 0.0001) compared with 1.8% among those who did not require dialysis. Variables that were significantly associated with the development of ARF by multivariate analysis included: increased age, elevated preoperative serum Cr, duration of CPB, presence of a carotid artery bruit, presence of diabetes, reduced cardiac ejection fraction and increased body weight. Variables independently associated with ARF-D included serum Cr, duration of CPB, carotid artery bruit and presence of diabetes. The utility of these models for predicting the development of ARF and ARF-D was confirmed by bootstrapping techniques. Because of the small number of patients who underwent valve surgery, none of these variables were significantly associated with the development of ARF or ARF-D in this group of patients. CONCLUSION: The development of ARF or ARF-D is associated with a high mortality following CABG surgery. We have identified perioperative variables, which may be useful in stratifying risk for the development of ARF.

Acute Kidney Injury↗
PubMed1999

The use of a postoperative morbidity survey to evaluate patients with prolonged hospitalization after routine, moderate-risk, elective surgery.

UNLABELLED: Vital healthcare resources are devoted to caring for patients with prolonged hospitalization after routine, moderate-risk surgery. Despite the significant cost, little is known about the overall incidence and pattern of complications in these patients. Four hundred thirty-eight patients undergoing a diverse group of routine, moderate-risk, elective surgical procedures were enrolled into a prospective, blinded, cohort study. Complications were assessed using a postoperative morbidity survey. The main outcome was postoperative complication, defined as either in-hospital death or prolonged postoperative hospitalization (> 7 days). The mortality rate was 1.6%. Postoperative complications occurred in 118 patients (27% [95% CI 23-31]). Complications frequently observed in these patients included: gastrointestinal 51% (42-60), pulmonary 25% (17-33), renal 21% (14-28), and infectious 13% (7-19). Most complications were not directly related to the type/site of surgery. Indices of tissue trauma (blood loss [P < 0.001], surgical duration [P = 0.001]) and tissue perfusion (arterial base deficit [P = 0.008], gastric pHi [P = 0.02]) were the strongest intraoperative predictors of complications. Despite a low mortality rate, we found that complications after routine, moderate-risk, elective surgery are common and involve multiple organ systems. Our 9-point survey can be used by healthcare providers and payers to characterize post-operative morbidity in their respective settings. IMPLICATIONS: Little is known about the overall incidence and pattern of complications in patients with prolonged hospitalization after routine, elective surgery. We prospectively assessed these complications using a novel postoperative morbidity survey. The postoperative morbidity survey can be used in future clinical outcome trials, as well as in routine hospital-based quality assurance.

Data Collection↗
PubMed1999

Ineffectiveness of burst suppression therapy in mitigating perioperative cerebrovascular dysfunction. Multicenter Study of Perioperative Ischemia (McSPI) Research Group.

BACKGROUND: Cerebral injury is among the most common and disabling complications of open heart surgery. Attempts to provide neuroprotection have yielded conflicting results. We assessed the potential of propofol-induced burst suppression during open heart surgery to provide cerebral protection as determined by postoperative neuropsychologic function. METHODS: Two hundred twenty-five patients undergoing valve surgery were randomized to receive either sufentanil or sufentanil plus propofol titrated to electroencephalographic burst suppression. Blinded investigators performed neurologic and neuropsychologic testing at baseline, postoperative day (POD) 1 (neurologic testing only), PODs 5-7, and PODs 50-70. Neuropsychologic tests were compared with the results of 40 nonsurgical patients matched for age and education. RESULTS: Electroencephalographic burst suppression was successfully achieved in all 109 propofol patients. However, these patients sustained at least as many adverse neurologic outcomes as the 116 controls: POD 1, 40% versus 25%, P = 0.06; PODs 5-7, -18% versus 8%, P = 0.07; PODs 50-70, -6% versus 6%, P = 0.80. No differences in the incidence of neuropsychologic deficits were detected, with 91% of the propofol patients versus 92% of the control patients being impaired at PODs 5-7, decreasing to 52 and 47%, respectively, by PODs 50-70. No significant differences in the severity of neuropsychologic dysfunction, depression, or anxiety were noted. CONCLUSIONS: Electroencephalographic burst suppression surgery with propofol during cardiac valve replacement did not significantly reduce the incidence or severity of neurologic or neuropsychologic dysfunction. The authors' results suggest that neither cerebral metabolic suppression nor reduction in cerebral blood flow reliably provide neuroprotection during open heart surgery. Other therapeutic approaches must be evaluated to address this important medical problem.

Adult↗
PubMed1999

Cerebral injury after cardiac surgery: identification of a group at extraordinary risk. Multicenter Study of Perioperative Ischemia Research Group (McSPI) and the Ischemia Research Education Foundation (IREF) Investigators.

BACKGROUND AND PURPOSE: Cerebral injury after cardiac surgery is now recognized as a serious and costly healthcare problem mandating immediate attention. To effect solution, those subgroups of patients at greatest risk must be identified, thereby allowing efficient implementation of new clinical strategies. No such subgroup has been identified; however, patients undergoing intracardiac surgery are thought to be at high risk, but comprehensive data regarding specific risk, impact on cost, and discharge disposition are not available. METHODS: We prospectively studied 273 patients enrolled from 24 diverse US medical centers, who were undergoing intracardiac and coronary artery surgery. Patient data were collected using standardized methods and included clinical, historical, specialized testing, neurological outcome and autopsy data, and measures of resource utilization. Adverse outcomes were defined a priori and determined after database closure by a blinded independent panel. Stepwise logistic regression models were developed to estimate the relative risks associated with clinical history and intraoperative and postoperative events. RESULTS: Adverse cerebral outcomes occurred in 16% of patients (43/273), being nearly equally divided between type I outcomes (8.4%; 5 cerebral deaths, 16 nonfatal strokes, and 2 new TIAs) and type II outcomes (7.3%; 17 new intellectual deterioration persisting at hospital discharge and 3 newly diagnosed seizures). Associated resource utilization was significantly increased--prolonging median intensive care unit stay from 3 days (no adverse cerebral outcome) to 8 days (type I; P<0.001) and from 3 to 6 days (type II; P<0.001), and increasing hospitalization by 50% (type II, P=0.04) to 100% (type I, P<0.001). Furthermore, specialized care after hospital discharge was frequently necessary in those with type I outcomes, in that only 31% returned home compared with 85% of patients without cerebral complications (P<0.001). Significant risk factors for type I outcomes related primarily to embolic phenomena, including proximal aortic atherosclerosis, intracardiac thrombus, and intermittent clamping of the aorta during surgery. For type II outcomes, risk factors again included proximal aortic atherosclerosis, as well as a preoperative history of endocarditis, alcohol abuse, perioperative dysrhythmia or poorly controlled hypertension, and the development of a low-output state after cardiopulmonary bypass. CONCLUSIONS: These prospective multicenter findings demonstrate that patients undergoing intracardiac surgery combined with coronary revascularization are at formidable risk, in that 1 in 6 will develop cerebral complications that are frequently costly and devastating. Thus, new strategies for perioperative management--including technical and pharmacological interventions--are now mandated for this subgroup of cardiac surgery patients.

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