Biomedical subjects

M Hollenberg

Publications and source records attributed to M Hollenberg.

At least 19 recordsLinked to original sources

PubMed2004

Agonists of proteinase-activated receptor-2 modulate human neutrophil cytokine secretion, expression of cell adhesion molecules, and migration within 3-D collagen lattices.

Proteinase-activated receptor-2 (PAR2) belongs to a novel subfamily of G-protein-coupled receptors with seven-transmembrane domains. PAR2 can be activated by serine proteases such as trypsin, mast cell tryptase, and allergic or bacterial proteases. This receptor is expressed by various cells and seems to be crucially involved during inflammation and the immune response. As previously reported, human neutrophils express functional PAR2. However, the precise physiological role of PAR2 on human neutrophils and its implication in human diseases remain unclear. We demonstrate that PAR2 agonist-stimulated human neutrophils show significantly enhanced migration in 3-D collagen lattices. PAR2 agonist stimulation also induced down-regulation of L-selectin display and up-regulation of membrane-activated complex-1 very late antigen-4 integrin expression on the neutrophil cell surface. Moreover, PAR2 stimulation results in an increased secretion of the cytokines interleukin (IL)-1beta, IL-8, and IL-6 by human neutrophils. These data indicate that PAR2 plays an important role in human neutrophil activation and may affect key neutrophil functions by regulating cell motility in the extracellular matrix, selectin shedding, and up-regulation of integrin expression and by stimulating the secretion of inflammatory mediators. Thus, PAR2 may represent a potential therapeutic target for the treatment of diseases involving activated neutrophils.

Calcium↗

PubMed2000

Oxygen uptake efficiency slope: an index of exercise performance and cardiopulmonary reserve requiring only submaximal exercise.

OBJECTIVES: We sought to evaluate, in adults, the efficacy of the Oxygen Uptake Efficiency Slope (OUES), an index of cardiopulmonary functional reserve that can be based upon a submaximal exercise effort. BACKGROUND: Maximal oxygen uptake (VO2,max), the most reliable measure of exercise capacity, is seldom attained in standard exercise testing. The OUES, which relates oxygen uptake to total ventilation during exercise, was proposed by Baba and coworkers (7) in a study of pediatric cardiac patients. They felt this submaximal index of cardiopulmonary reserve might be more practical than VO2max and more appropriate than the commonly used peak oxygen consumption (VO2 peak). METHODS: Treadmill exercise tests with simultaneous respiratory gas measurement were performed in 998 older subjects free of clinically recognized cardiovascular disease and 12 male patients with congestive heart failure. During incremental exercise, oxygen uptake was plotted against the logarithm of total ventilation, and the OUES was determined. RESULTS: The OUES, when calculated only from the first 75% of the exercise test, differed by 1.9% from the OUES calculated from 100% of exercise time in subjects with a peak respiratory exchange rate > or =1.10. On serial tests the OUES was less variable than exercise duration or VO2 peak. It correlated strongly with VO2max, with forced expiratory volume in 1 s and negatively with a history of current smoking. The OUES declined linearly with age in both women and men. A small sample of patients with congestive heart failure had OUES values much lower than those of older subjects without cardiovascular disease. CONCLUSIONS: The OUES is an objective, reproducible measure of cardiopulmonary reserve that does not require a maximal exercise effort. It integrates cardiovascular, musculoskeletal and respiratory function into a single index that is largely influenced by pulmonary dead space ventilation and exercise-induced lactic acidosis.

Aged↗

PubMed1999

Design and synthesis of thrombin receptor-derived nonpeptide mimetics utilizing a piperazine scaffold.

Focal thrombus formation and vasoconstriction serve to defend vessels when vascular damage occurs, but may be detrimental when an atherosclerotic plaque is disrupted. Recently, the identification of the platelet thrombin receptor opened a new area in the development of agents that may selectively inhibit the effects of thrombin on cells, without affecting fibrin formation. In this regard, we have synthesized a number of 1,4-disubstituted piperazines which are designed to be analogues of thrombin receptor activating peptides (TRAP) and carry the pharmacophoric features of Phe and Arg residues present in the active pentapeptide SFLLR. These compounds were tested in the rat aorta relaxation assay and in platelet aggregation studies and their biological activity was consistent with a direct action on thrombin receptor. Furthermore, the structure activity relationships confirmed the importance of Phe and Arg for receptor activation and the molecular modeling revealed an intriguing relationship between their amphipathic similarity with SFLLR and their biological activity.

Animals↗

PubMed1998

Association between self-reported leisure-time physical activity and measures of cardiorespiratory fitness in an elderly population.

Leisure-time physical activity enhances health and functioning in older populations. However, few data are available on the correlation between self-reported leisure-time physical activity and cardiorespiratory fitness in the elderly. Treadmill exercise testing results were obtained for 1,006 members (median age 67 years) of a community-based sample. Subjects completed a standardized evaluation of medical/social history and measures of physical function. Leisure-time physical activity in the 12 months and 7 days before interview and over subjects' lifetimes was summarized as total and activity-specific METs/week and [METs * (hours/week)]. Multiple linear regression was used to investigate the cross-sectional, sex-specific associations between peak oxygen consumption (VO2) and exercise duration. After adjustment for age, body mass index, smoking history, medical morbidity, direct measures of physical functioning, forced expiratory volumes, and maximum respiratory muscle pressure, leisure-time physical activity accounted for < or = 5% of the variance of VO2 and exercise duration. Results were unchanged when analyses were restricted to subjects who achieved high levels of exercise. These data indicate that measures of aerobic capacity cannot be used to "validate" self-reported leisure-time physical activity in older subjects, and they further suggest that beneficial effects of physical activity in the elderly are the result of metabolic effects that are not reflected well by maximal aerobic capacity during exercise testing.

Age Distribution↗

PubMed1998

Prophylactic atenolol reduces postoperative myocardial ischemia. McSPI Research Group.

BACKGROUND: Perioperative myocardial ischemia occurs in 20-40% of patients at risk for cardiac complications and is associated with a ninefold increase in risk for perioperative cardiac death, myocardial infarction, or unstable angina, and a twofold long-term risk. Perioperative atenolol administration reduces the risk of death for as long as 2 yr after surgery. This randomized, placebo-controlled, double-blinded trial tested the hypothesis that perioperative atenolol administration reduces the incidence and severity of perioperative myocardial ischemia, potentially explaining the observed reduction in the risk for death. METHODS: Two-hundred patients with, or at risk for, coronary artery disease were randomized to two study groups (atenolol and placebo). Monitoring included a preoperative history and physical examination and daily assessment of any adverse events. Twelve-lead electrocardiography (ECG), three-lead Holter ECG, and creatinine phosphokinase with myocardial banding (CPK with MB) data were collected 24 h before until 7 days after surgery. Atenolol (0, 5, or 10 mg) or placebo was administered intravenously before induction of anesthesia and every 12 h after operation until the patient could take oral medications. Atenolol (0, 50, or 100 mg) was administered orally once a day as specified by blood pressure and heart rate. RESULTS: During the postoperative period, the incidence of myocardial ischemia was significantly reduced in the atenolol group: days 0-2 (atenolol 17 of 99 patients; placebo, 34 of 101 patients; P = 0.008) and days 0-7 (atenolol, 24 of 99 patients; placebo, 39 of 101 patients; P = 0.029). Patients with episodes of myocardial ischemia were more likely to die in the next 2 yr (P = 0.025). CONCLUSIONS: Perioperative administration of atenolol for 1 week to patients at high risk for coronary artery disease significantly reduces the incidence of postoperative myocardial ischemia. Reductions in perioperative myocardial ischemia are associated with reductions in the risk for death at 2 yr.

Adrenergic beta-Antagonists↗

PubMed1997

Electrocardiographic and hemodynamic changes and their association with myocardial infarction during coronary artery bypass surgery. A multicenter study. Multicenter Study of Perioperative Ischemia (McSPI) Research Group.

BACKGROUND: Electrocardiographic (ECG) changes during coronary artery bypass graft surgery have not been described in detail in a large multicenter population. The authors describe these ECG changes and evaluate them, along with demographic and clinical characteristics and intraoperative hemodynamic alterations, as predictors of myocardial infarction (MI) as defined by two sets of criteria. METHODS: Data from 566 patients at 20 clinical sites, collected as part of a clinical trial to evaluate the efficacy of acadesine for reducing MI, were analyzed at core laboratories. Perioperative ECG changes were identified using continuous three-lead Holter ECG. Systolic blood pressure, diastolic blood pressure, and heart rate were recorded each minute during operation. The occurrence of MI by Q wave or myocardial fraction of creatine kinase (CK-MB) or autopsy criteria, and by (Q wave and CK-MB) or autopsy criteria was determined. RESULTS: During perioperative Holter monitoring, episodes of ST segment deviation, major cardiac conduction changes > or = 30 min, or use of ventricular pacing > or = 30 min occurred in 58% patients, primarily in the first 8 h after release of aortic occlusion. Of the 25% patients who met the Q wave or CK-MB or autopsy criteria for MI, 19% had increased CK-MB as well as ECG changes. (Q wave and CK-MB) or autopsy criteria for MI were met by 4% of patients. The CK-MB concentration generally peaked by 16 h after release of aortic occlusion. In patients with (n = 187) and without a perioperative episode of ST segment deviation, the incidence of MI was 36% and 19%, respectively (P < 0.01), by Q wave or CK-MB or autopsy criteria, and 6% and 3%, respectively (P = 0.055), by (Q wave and CK-MB) or autopsy criteria. Multiple logistic regression analysis showed that intraoperative ST segment deviation, intraventricular conduction defect, left bundle branch block, duration of hypotension (systolic blood pressure < 90 mmHg) after cardiopulmonary bypass, and duration of cardiopulmonary bypass are independent predictors of Q wave or CK-MB or autopsy MI. The independent predictors of (Q wave and CK-MB) or autopsy MI are intraoperative ST segment deviation and duration of aortic occlusion. CONCLUSIONS: Major ECG changes occurred in 58% of patients during coronary artery bypass graft surgery, primarily within 8 h after release of aortic occlusion. Multicenter data collection revealed a substantial variation in the incidence of MI and an overall incidence of up to 25%, with most MI occurring within 16 h after release of aortic occlusion. Intraoperative monitoring of ECG and hemodynamics has incremental value for predicting MI.

Aged↗

PubMed1995

Effects of perioperative dexmedetomidine infusion in patients undergoing vascular surgery. The Study of Perioperative Ischemia Research Group.

BACKGROUND: Dexmedetomidine, a highly selective alpha 2-adrenergic agonist, increases perioperative hemodynamic stability in healthy patients but decreases blood pressure and heart rate. The goal of this study was to evaluate, in a preliminary manner, the hemodynamic effects of perioperatively administered dexmedetomidine in surgical patients at high risk for coronary artery disease. METHODS: Twenty-four vascular surgery patients received a continuous infusion of placebo or one of three doses of dexmedetomidine, targeting plasma concentrations of 0.15 ng/ml (low dose), 0.30 ng/ml (medium dose), or 0.45 ng/ml (high dose) from 1 h before induction of anesthesia until 48 h postoperatively. All patients received standardized anesthesia and hemodynamic management. Blood pressure, heart rate, and Holter ECG were monitored; additional monitoring included continuous 12-lead ECG preoperatively, anesthetic concentrations and myocardial wall motion (echocardiography) intraoperatively, and cardiac enzymes postoperatively. RESULTS: Preoperatively, there was a decrease in heart rate (low dose 11%, medium dose 5%, high dose 20%) and systolic blood pressure (low dose 3%, medium dose 12%, high dose 20%) in patients receiving dexmedetomidine. Intraoperatively, dexmedetomidine groups required more vasoactive medications to maintain hemodynamics within predetermined limits. Postoperatively, demedetomidine groups had less tachycardia (minutes/monitored hours) than the placebo group (placebo 23 min/h; low dose 9 min/h, P = 0.006; medium dose 0.5 min/h, P = 0.004; high dose 2.3 min/h, P = 0.004). Bradycardia was rare in all groups. There were no myocardial infarctions or discernible trends in the laboratory results. CONCLUSIONS: Infusion of dexmedetomidine up to a targeted plasma concentration of 0.45 ng/ml appears to benefit perioperative hemodynamic management of surgical patients undergoing vascular surgery but required greater intraoperative pharmacologic intervention to support blood pressure and heart rate.

Blood Pressure↗

PubMed1994

Therapeutic approaches to postoperative ischemia. The Study of Perioperative Ischemia Research Group.

Previous attempts to identify predictors of cardiac complications, an important cause of postoperative morbidity and mortality following non-cardiac surgery, have focused mainly on the patient's preoperative state. Our research group, however, has found that adverse cardiac outcome correlates most highly with the appearance of at least 1 ischemic episode determined by continuous ambulatory electrocardiographic monitoring (AEM) in the early postoperative period. Such early postoperative ischemia conferred (1) a greater than 9-fold increased risk of experiencing in-hospital cardiac death, nonfatal myocardial infarction, or postoperative unstable angina, and (2) a greater than 2-fold increased long-term (2-year) risk of cardiac death, myocardial infarction, or angina requiring coronary angioplasty or coronary artery bypass grafting (CABG). Additionally, 5 predictors of such postoperative ischemia were identified: left ventricular hypertrophy, diabetes mellitus, hypertension, definite coronary artery disease, and preoperative digoxin use. These findings suggest that patients who are at high risk for postoperative myocardial ischemia warrant more intensive postoperative monitoring. Moreover, since such ischemia is potentially reversible, the testing of strategies designed to prevent or manage postoperative ischemia appears warranted and is discussed. Our group also has established the usefulness of AEM for identifying ischemic episodes in patients undergoing CABG. However, patients who require cardiopulmonary bypass present unique problems regarding the interpretation of AEM recordings. We describe guidelines for the interpretation of AEM results obtained under these conditions and suggest criteria based on the degree of interpretability for patient inclusion in future studies.

Cardiopulmonary Bypass↗

PubMed1994

Reliability of the continuous ECG after cardiopulmonary bypass and CABG surgery.

Because of ECG changes associated with phenomena such as myocardial stunning or reperfusion injury in patients undergoing coronary artery bypass graft (CABG) surgery, Holter recordings may not detect postoperative myocardial ischemia with the same sensitivity and accuracy achieved in patients undergoing noncardiac surgery. This study details the reasons for decreased sensitivity of Holter recordings under such circumstances and suggests guidelines for inclusion of patients undergoing CABG into future studies. Continuous ECG (Holter) recordings were obtained in 617 analyzable patients before, during, and for 24 to 48 hours after CABG surgery. Uninterpretable tracings occurred with greatest frequency in the immediate period after electrical defibrillation and decreased progressively thereafter; only 50% of recorded tracings were interpretable and the percent of interpretable recordings increased progressively for the next 9 hours and then remained constant. This study confirmed the great frequency with which ECG abnormalities occur in the early postoperative period following bypass or coronary artery revascularization; it supports the suitability of Holter monitoring in patients who undergo cardiopulmonary bypass and CABG only if rigorous criteria for ECG interpretability and patient exclusion are used. In addition, because precise data were available for analysis for two thirds of all recruited patients, these results should provide valuable guidelines for estimating the appropriate sample size in the design of future studies similar to this one.

Cardiopulmonary Bypass↗

PubMed1994

An initial multicenter, randomized controlled trial on the safety and efficacy of acadesine in patients undergoing coronary artery bypass graft surgery. SPI Research Group.

Acadesine (5-amino-4-imidazole carboxamide riboside) is a purine nucleoside analog that has been shown in animals to reduce myocardial ischemic injury by selectively increasing the availability of adenosine in ischemic tissues. Because patients undergoing coronary artery bypass graft (CABG) surgery are especially vulnerable to developing myocardial ischemia, we investigated whether perioperative use of this adenosine-regulating drug with potential anti-ischemic properties could modify the incidence and severity of perioperative myocardial ischemia. The goals of this study were to evaluate safety and the effects of acadesine on myocardial ischemia, left ventricular function, and, secondarily, on adverse clinical outcomes (myocardial infarction, heart failure, life-threatening dysrhythmias, and death) in patients undergoing CABG surgery. One hundred sixteen patients were randomized to receive one of three continuous intravenous dosing regimens (placebo [control] or one of two doses of acadesine [high- and low-dose infusion]) in double-blind fashion intraoperatively and in the early postoperative period (total infusion time was 7 h). Multidose cold crystalloid cardioplegia (each containing either acadesine or placebo) was used for myocardial protection. All were monitored for potentially drug-related adverse events and the presence of myocardial ischemia was assessed by continuous Holter electrocardiography (ECG) and transesophageal echocardiography (TEE). All patients received standardized anesthetic, surgical, and hemodynamic management during the intraoperative period. All research data (ECG, TEE, outcome data) were evaluated at the coordinating center (San Francisco) in blinded fashion to ensure that uniform data analysis criteria were employed. The administration of acadesine was safe: mild increases in plasma uric acid (a metabolite of acadesine) occurred only in patients receiving high doses (mean increase 1.6 +/- 0.2 mg/dL) and were without clinical sequelae. Before drug administration in the preoperative period (baseline), the incidence and severity of ECG ischemia did not differ among the three groups (placebo = 18%; low-dose = 14%; high-dose = 14%). During prebypass, the incidence of ECG ischemia was similar in all three groups (0%, 3%, 3%, respectively). The incidence of TEE ischemia was numerically lower in the two acadesine groups (high-dose = 6%, low-dose = 15%) than in the control group (19%), but this was not statistically significant (P = 0.22). During postbypass, the incidence of ECG ischemia was 11% in the high-dose group, 22% in the low-dose group, and 18% in the control group (P = 0.42), and TEE ischemia was similar in incidence in all groups (placebo = 29%; low dose = 27%; high-dose = 24%) (P = 0.86).(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

PubMed1992

Effects of steal-prone anatomy on intraoperative myocardial ischemia. The SPI Research Group.

OBJECTIVES: Our study objective was to determine whether the presence of steal-prone anatomy conferred an increased risk in the development of intraoperative myocardial ischemia. BACKGROUND: Coronary artery steal of collateral blood flow has been demonstrated for many vasodilators, including isoflurane, the most commonly used inhalational anesthetic agent in the United States. It has been postulated that patients with steal-prone anatomy (total occlusion of one coronary artery that is supplied distally by collateral flow from another coronary artery with a > or = 50% stenosis) may be particularly at risk for the development of intraoperative myocardial ischemia when an anesthetic with a vasodilator property is being administered. METHODS: We evaluated the risk of myocardial ischemia under isoflurane anesthesia (vs. a high dose narcotic technique using sufentanil) using continuous intraoperative electrocardiography and transesophageal echocardiography in patients with and without steal-prone anatomy undergoing coronary artery bypass graft surgery. RESULTS: Sixty-two (33%) of the 186 patients had steal-prone anatomy: in 5 (8%) the collateral-supplying vessel was > or = 50% to 69% stenosed, in 24 (39%) it was > or = 70% to 89% stenosed and in 33 (53%) it was > or = 90% stenosed. The incidence of ischemia (transesophageal echocardiography or intraoperative electrocardiography, or both) was similar in patients with and without steal-prone coronary anatomy (18 [29%] of 62 patients vs. 39 [31%] of 124 patients, p = 0.87, 95% confidence interval = -0.13 to 0.17). The incidence of intraoperative ischemia was similar in patients who received isoflurane or sufentanil anesthesia (20 [32%] of 62 patients vs. 37 [30%] of 124 patients, p = 0.87). The incidence of tachycardia and hypotension was low (increases in heart rate = 9.8%, and decreases in systolic blood pressure = 10.8% of total monitoring time during the prebypass period compared with preoperative baseline values). The incidence of adverse cardiac outcome was similar in patients with and without preoperative steal-prone coronary anatomy (4 [7%] of 62 patients vs. 14 [11%] of 124 patients, p = 0.53). CONCLUSIONS: These findings demonstrate that under strict hemodynamic control the presence of steal-prone anatomy does not confer an increased risk in the development of intraoperative myocardial ischemia.

Adult↗

PubMed1992

Monitoring for myocardial ischemia during noncardiac surgery. A technology assessment of transesophageal echocardiography and 12-lead electrocardiography. The Study of Perioperative Ischemia Research Group.

OBJECTIVE: Transesophageal echocardiography (TEE) and 12-lead electrocardiography (ECG) are sophisticated techniques that are increasingly being used to monitor for myocardial ischemia during noncardiac surgery. We examined whether the routine use of these techniques has incremental clinical value in identifying patients at high risk for perioperative ischemic outcomes when compared with preoperative clinical data and intraoperative monitoring using continuous two-lead bipolar ECG. DESIGN: Cohort study. SETTING: Veterans Affairs medical center. PATIENTS: A total of 332 men undergoing noncardiac surgery who had or were at high risk for coronary artery disease. INTERVENTIONS: TEE, 12-lead ECG, and two-lead ECG were performed continuously during noncardiac surgery (47% vascular, 53% nonvascular). Monitoring results were not available to anesthesiologists or surgeons, and data were blindly analyzed after surgery. MAIN OUTCOME MEASURE: Perioperative ischemic outcomes (cardiac death, nonfatal myocardial infarction, unstable angina). RESULTS: In a subset of 285 patients who were adequately studied by all three techniques, 111 patients (39%) were identified as having intraoperative myocardial ischemia (by one or more monitoring techniques). By univariate analysis, intraoperative ischemia was associated with all perioperative cardiac outcomes, including ischemic outcomes, congestive heart failure, and ventricular tachycardia (P less than or equal to .02 for each of the three monitoring techniques). However, when monitoring results for TEE and 12-lead ECG were added to a multivariate model that included preoperative clinical data and continuous two-lead ECG results, the incremental value of TEE was small (odds ratio, 2.6; 95% confidence interval [CI], 1.2 to 5.7; P = .02) and that of 12-lead ECG was not significant (odds ratio, 1.5; 95% CI, 0.6 to 3.8). Furthermore, when the multivariate analysis was repeated with only ischemic outcomes, neither TEE nor 12-lead ECG retained significant associations (odds ratio, 2.2; 95% CI, 0.5 to 9.4, and odds ratio, 1.1; 95% CI, 0.2 to 6.1, respectively). CONCLUSION: When compared with preoperative clinical data and intraoperative monitoring using two-lead ECG, routine monitoring for myocardial ischemia with TEE or 12-lead ECG during noncardiac surgery has little incremental clinical value in identifying patients at high risk for perioperative ischemic outcomes.

Aged↗

PubMed1992

Long-term cardiac prognosis following noncardiac surgery. The Study of Perioperative Ischemia Research Group.

OBJECTIVE: To determine the long-term (2-year) cardiac prognosis of high-risk patients undergoing noncardiac surgery and to determine the predictors of long-term adverse cardiac outcome. DESIGN: Prospective cohort study. Historical, clinical, and laboratory data were collected during the in-hospital period, and at 6 months, 1 year, and 2 years following surgery. Data were analyzed using proportional hazards models. SETTING: University-affiliated Veterans Affairs medical center. POPULATION: A consecutive sample of 444 patients with or at high risk for coronary artery disease who had undergone elective noncardiac surgery and were discharged from the hospital in stable condition. MAIN OUTCOME MEASURES: Cardiac death, myocardial infarction, unstable angina, progressive angina requiring coronary artery bypass graft surgery or coronary angioplasty, and new unstable angina requiring hospitalization. RESULTS: Forty-seven patients (11%) had major cardiovascular complications during a 728-day (median) follow-up period: 24 had cardiac death; 11, nonfatal myocardial infarction; six, progressive angina requiring coronary artery bypass graft surgery or coronary angioplasty; and six, new unstable angina requiring hospitalization. Thirty percent of outcomes occurred within 6 months of surgery and 64% within 1 year. Five independent predictors of long-term outcome were identified. Three predictors reflected the preexisting chronic disease state: (1) the presence of known vascular disease (hazard ratio, 6.1; 95% confidence interval [CI], 2.5 to 15.0; P less than .0001); (2) a history of congestive heart failure (hazard ratio, 5.0; 95% CI, 2.0 to 12.0; P less than .0005); and (3) known coronary artery disease (hazard ratio, 3.7; 95% CI, 1.7 to 8.0; P less than .0007). Two predictors reflected acute postoperative ischemic events: (1) myocardial infarction/unstable angina (hazard ratio, 20; 95% CI, 7.5 to 53.0; P less than .0001) and (2) myocardial ischemia (hazard ratio, 2.2; 95% CI, 1.1 to 4.3; P less than .03). Patients surviving a postoperative in-hospital myocardial infarction had a 28-fold increase in the rate of subsequent cardiac complications within 6 months following surgery, a 15-fold increase within 1 year, and a 14-fold increase within 2 years (95% CI, 5.8 to 32; P less than .00001). Seventy percent of all long-term adverse outcomes were preceded by in-hospital postoperative ischemia that occurred at least 30 days (median, 282 days) before the long-term event. The development of congestive heart failure or ventricular tachycardia (without ischemia) during hospitalization was not associated with adverse long-term outcome. CONCLUSIONS: The incidence of long-term adverse cardiac outcomes following noncardiac surgery is substantial. At increased risk are patients with chronic cardiovascular disease; at highest risk are patients with acute perioperative ischemic events. We conclude that survivors of in-hospital perioperative ischemic events, specifically myocardial infarction, unstable angina, and postoperative ischemia, warrant more aggressive long-term follow-up and treatment than is currently practiced.

Acute Disease↗

PubMed1992

Predictors of postoperative myocardial ischemia in patients undergoing noncardiac surgery. The Study of Perioperative Ischemia Research Group.

OBJECTIVE: To identify predictors of postoperative myocardial ischemia in patients scheduled to undergo major noncardiac surgery. DESIGN: Historical, clinical, laboratory, and physiological data were obtained prospectively before and during surgery to identify potential univariate predictors of postoperative myocardial ischemia, which then were entered into multivariate logistic models. Continuous two-lead electrocardiograms before, during, and after surgery were used to identify episodes of myocardial ischemia. SETTING: Department of Veterans Affairs tertiary care hospital. PATIENTS: A consecutive sample of 474 men at high risk for or with coronary artery disease who were scheduled to undergo major noncardiac surgery (95% compliance rate). MAIN OUTCOME MEASURE: Significant variables identified by multivariate logistic models that are associated with postoperative myocardial ischemia. RESULTS: Five major preoperative predictors of postoperative myocardial ischemia were identified: (1) left ventricular hypertrophy by electrocardiogram; (2) history of hypertension; (3) diabetes mellitus; (4) definite coronary artery disease; and (5) use of digoxin. The risk of postoperative myocardial ischemia increased progressively with the number of predictors present: in 22% of patients with no predictors, in 31% with one predictor, in 46% with two predictors, in 70% with three predictors, and in 77% with four predictors. CONCLUSION: Patients subgroups who are at high risk for developing postoperative myocardial ischemia and who might benefit the most from intensive Holter monitoring in the postoperative period now can be identified preoperatively.

Aged↗

PubMed1992

Postoperative myocardial ischemia. Therapeutic trials using intensive analgesia following surgery. The Study of Perioperative Ischemia (SPI) Research Group.

Recent data suggest that postbypass and postoperative myocardial ischemia are related to adverse cardiac outcome following myocardial revascularization. Therapeutic trials to suppress postoperative ischemia are warranted. Because anesthetics can suppress a variety of physiologic responses to stress as well as myocardial ischemia intraoperatively, we examined whether use of intensive analgesia in the stressful postoperative period could decrease postoperative ischemia. In 106 patients undergoing elective myocardial revascularization, we standardized the anesthetic prior to bypass (sufentanil 5-10 micrograms/kg [induction] and 4.2-6.0 micrograms.kg-1.h-1 [infusion] supplemented with up to 0.5 mg/kg of diazepam). During bypass, patients were randomly assigned to receive either morphine sulfate (group M, n = 54, up to 2 mg/kg) or sufentanil (group S, n = 52, 1 microgram/kg and 1 microgram.kg-1.h-1). In the intensive care unit (ICU), group M received low-dose analgesia (morphine sulfate 1-10 mg intravenously every 30 min, average dose = 2.2 +/- 2.1 mg/h), while group S continued to receive intensive analgesia (infusion of sufentanil at 1 microgram.kg-1.h-1). Both groups received supplemental midazolam in the ICU (group M = 1.1 +/- 1.1 mg/h; group S = 0.6 +/- 0.6 mg/h; P = 0.01). All analgesic and sedative-hypnotic medications were discontinued at 18 hours following myocardial revascularization. Using continuous two-channel electrocardiographic (ECG) monitoring (CC5 and CM5), we documented and characterized ECG changes consistent with ischemia during the preoperative, intraoperative (pre- and postbypass), and postoperative (on- and off-treatment) periods. The total ECG monitoring time was 8,486 h, averaging 81 h per patient. During the prebypass (anesthetic control) period, groups M and S had a similar incidence, but group S episodes were more severe: maximum ST-segment change (median), S versus M: -1.8 mm versus -1.4 mm (P = 0.04). During the postbypass period, both groups had a similar incidence of ischemia, but episodes in group S were less severe: maximum ST-segment change, S versus M: -1.8 mm versus -2.7 mm (P = 0.0005). During the ICU-on-therapy period, the incidence of ischemic episodes was less in group S patients, and the severity was less: area-under-the-ST-time curve, S versus M: -21 mm.min versus -161 mm.min (P = 0.05). After discontinuation of the drug regimen in the ICU, the incidence and severity of ischemic episodes was similar. The incidence of hypotension, hypertension, and tachycardia was similar in both groups in both the intraoperative and ICU periods.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1991

Modulation of the beta-adrenergic-response in cultured rat heart cells. II. Mammary-derived growth inhibitor (MDGI) blocks induction of beta-adrenergic supersensitivity. Dissociation from lipid-binding activity of MDGI.

'Mammary-derived growth inhibitor (MDGI)' is a 14.5 kDa polypeptide with growth-inhibitory activity for various mammary epithelial cells in vitro which is highly homologous to cardiac fatty acid-binding protein (H-FABP). Here we describe a new biological activity of MDGI: Inhibition of L(+)-lactate-, arachidonic acid- and 15-S-hydroxyeicosatetraenoic acid-induced supersensitivity of neonatal rat heart cells for beta-adrenergic stimulation, concerning particularly a small population of beta 2-receptors. Synthetic peptides corresponding to the MDGI-sequence, residue 121-131 mimic the effect of MDGI. Measurements of lipid-binding to MDGI and synthetic peptides excluded the binding of arachidonic acid, 15-S-hydroxyeicosatetraenoic acid or beta-adrenergic agonists to MDGI or the peptides as the mechanism for this effect. Also, no direct interference of MDGI and the synthetic peptides with the binding of the beta-adrenergic agent CGP 12177 to its receptor on A431 cells could be detected. We suggest that MDGI and the peptides act by interference with the function of the beta 2-adrenergic receptor and that this mechanism might also be relevant for the growth-inhibitory activity of MDGI. Furthermore, the data point to a possible function of H-FABP for the modulation of beta-adrenergic sensitivity of cardiac myocytes.

Amino Acid Sequence↗

PubMed1991

Perioperative myocardial ischemia in patients undergoing noncardiac surgery--I: Incidence and severity during the 4 day perioperative period. The Study of Perioperative Ischemia (SPI) Research Group.

To determine the incidence and characteristics of perioperative myocardial ischemia, the electrocardiographic (ECG) changes consistent with ischemia during the 4 day perioperative period were documented and characterized in 100 patients with or at risk for coronary artery disease undergoing noncardiac surgery. Using continuous two channel ECG monitoring (leads CC5 and CM5), the frequency and severity of ECG ischemic episodes defined by ST segment depression greater than or equal to 1 mm or elevation greater than or equal to 2 mm during the preoperative (up to 2 days), intraoperative and early postoperative (first 2 days) periods were compared. Preoperatively, 28 patients (28%) exhibited 105 episodes of ischemia; intraoperatively, 27 patients exhibited 39 episodes and postoperatively, 42 patients exhibited 187 episodes. There was no difference between the pre- and intraoperative episode characteristics. However, postoperative ischemic episodes were the most severe. The mean ST change was 1.5, 2 and 2.6 mm for pre-, intra- and postoperative episodes, respectively (p less than 0.0001 postoperative versus pre- or intraoperative); duration of ischemic episodes was 69, 45 and 207 min, respectively (p less than 0.005 postoperative versus preoperative, p less than 0.001 versus intraoperative) and area under the ST curve was 88, 74 and 383 mm.min (p less than 0.009 postoperative versus preoperative, p less than 0.005 versus intraoperative). Ninety-four percent of all postoperative ischemic episodes were silent; 80% of all episodes occurred without acute change (+/- 20% of control) in heart rate and 77% of intraoperative episodes occurred without acute change in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1991

Dipyridamole thallium-201 scintigraphy as a preoperative screening test. A reexamination of its predictive potential. Study of Perioperative Ischemia Research Group.

BACKGROUND: We examined the value of dipyridamole thallium-201 (201Tl) scintigraphy as a preoperative screening test for perioperative myocardial ischemia and infarction. METHODS AND RESULTS: We prospectively studied 60 patients undergoing elective vascular surgery. We performed 201Tl scintigraphy preoperatively and blinded all treating physicians to the results. Historical, clinical, laboratory, and physiological data were gathered throughout hospitalization. Myocardial ischemia was assessed during the intraoperative period using continuous 12-lead electrocardiography (ECG) and transesophageal echocardiography (TEE) and during the postoperative period using continuous two-lead ambulatory ECG. Adverse cardiac outcomes (cardiac death, myocardial infarction, unstable angina, severe ischemia, or congestive heart failure) were assessed daily throughout hospitalization. Twenty-two patients (37%) had defects that improved or reversed on delayed scintigrams (redistribution defects), 18 (30%) had persistent defects, and 20 (33%) had no defects on 201Tl scintigraphy. There was no association between redistribution defects and adverse cardiac outcomes: 54% (seven of 13) of adverse outcomes occurred in patients without redistribution defects, and the risk of an adverse outcome was not significantly increased in patients with redistribution defects (relative risk 1.5, 95% confidence interval 0.6-3.9, p = 0.43). Consistent with these findings, there was also no association between redistribution defects and perioperative ischemia: 54% (19 of all 35) of perioperative ECG and TEE ischemic episodes and 58% (14 of 24) of severe ischemic episodes occurred in patients without redistribution defects. The sensitivity of 201Tl scintigraphy for perioperative ischemia and adverse outcomes ranged from 40% to 54%, specificity from 65% to 71%, positive predictive value from 27% to 47% and negative predictive value from 61% to 82%. CONCLUSIONS: These results differ from those of previous studies and suggest that the routine use of 201Tl scintigraphy for preoperative screening of patients undergoing vascular surgery may not be warranted.

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