Body morphology, energy stores, and muscle enzyme activity explain cricket acoustic mate attraction signaling variation.

High mating success in animals is often dependent on males signalling attractively with high effort. Since males should be selected to maximize their reproductive success, female preferences for these traits should result in minimal signal variation persisting in the population. However, extensive signal variation persists. The genic capture hypothesis proposes genetic variation persists because fitness-conferring traits depend on an individual's basic processes, including underlying physiological, morphological, and biochemical traits, which are themselves genetically variable. To explore the traits underlying signal variation, we quantified among-male differences in signalling, morphology, energy stores, and the activities of key enzymes associated with signalling muscle metabolism in two species of crickets, Gryllus assimilis (chirper: <20 pulses/chirp) and G. texensis (triller: >20 pulses/chirp). Chirping G. assimilis primarily fuelled signalling with carbohydrate metabolism: smaller individuals and individuals with increased thoracic glycogen stores signalled for mates with greater effort; individuals with greater glycogen phosphorylase activity produced more attractive mating signals. Conversely, the more energetic trilling G. texensis fuelled signalling with both lipid and carbohydrate metabolism: individuals with increased ß-hydroxyacyl-CoA dehydrogenase activity and increased thoracic free carbohydrate content signalled for mates with greater effort; individuals with higher thoracic and abdominal carbohydrate content and higher abdominal lipid stores produced more attractive signals. Our findings suggest variation in male reproductive success may be driven by hidden physiological trade-offs that affect the ability to uptake, retain, and use essential nutrients, although the results remain correlational in nature. Our findings indicate that a physiological perspective may help us to understand some of the causes of variation in behaviour.

Adaptive plasticity in wild field cricket's acoustic signaling.

Phenotypic plasticity can be adaptive when phenotypes are closely matched to changes in the environment. In crickets, rhythmic fluctuations in the biotic and abiotic environment regularly result in diel rhythms in density of sexually active individuals. Given that density strongly influences the intensity of sexual selection, we asked whether crickets exhibit plasticity in signaling behavior that aligns with these rhythmic fluctuations in the socio-sexual environment. We quantified the acoustic mate signaling behavior of wild-caught males of two cricket species, Gryllus veletis and G. pennsylvanicus. Crickets exhibited phenotypically plastic mate signaling behavior, with most males signaling more often and more attractively during the times of day when mating activity is highest in the wild. Most male G. pennsylvanicus chirped more often and louder, with shorter interpulse durations, pulse periods, chirp durations, and interchirp durations, and at slightly higher carrier frequencies during the time of the day that mating activity is highest in the wild. Similarly, most male G. veletis chirped more often, with more pulses per chirp, longer interpulse durations, pulse periods, and chirp durations, shorter interchirp durations, and at lower carrier frequencies during the time of peak mating activity in the wild. Among-male variation in signaling plasticity was high, with some males signaling in an apparently maladaptive manner. Body size explained some of the among-male variation in G. pennsylvanicus plasticity but not G. veletis plasticity. Overall, our findings suggest that crickets exhibit phenotypically plastic mate attraction signals that closely match the fluctuating socio-sexual context they experience.

Calling, courtship, and condition in the fall field cricket, Gryllus pennsylvanicus.

Theoretically, sexual signals should provide honest information about mating benefits and many sexually reproducing species use honest signals when signalling to potential mates. Male crickets produce two types of acoustic mating signals: a long-distance mate attraction call and a short-range courtship call. We tested whether wild-caught fall field cricket (Gryllus pennsylvanicus) males in high condition (high residual mass or large body size) produce higher effort calls (in support of the honest signalling hypothesis). We also tested an alternative hypothesis, whether low condition males produce higher effort calls (in support of the terminal investment hypothesis). Several components of long-distance mate attraction calls honestly reflected male body size, with larger males producing louder mate attraction calls at lower carrier frequencies. Long-distance mate attraction chirp rate dishonestly signalled body size, with small males producing faster chirp rates. Short-range courtship calls dishonestly reflected male residual mass, as chirp rate and pulse rate were best explained by a curvilinear function of residual mass. By producing long-distance mate attraction calls and courtship calls with similar or higher effort compared to high condition males, low condition males (low residual mass or small body size) may increase their effort in current reproductive success at the expense of their future reproductive success, suggesting that not all sexual signals are honest.

Prognostic implications of asymptomatic left ventricular dysfunction in patients undergoing vascular surgery.

BACKGROUND: The prognostic value of heart failure symptoms on postoperative outcome is well acknowledged in perioperative guidelines. The prognostic value of asymptomatic left ventricular (LV) dysfunction remains unknown. This study evaluated the prognostic implications of asymptomatic LV dysfunction in vascular surgery patients assessed with routine echocardiography. METHODS: Echocardiography was performed preoperatively in 1,005 consecutive vascular surgery patients. Systolic LV dysfunction was defined as LV ejection fraction less than 50%. Ratio of mitral-peak velocity during early and late filling, pulmonary vein flow, and deceleration time was used to diagnose diastolic LV dysfunction. Troponin-T measurements and electrocardiograms were performed routinely perioperatively. Multivariate regression analyses evaluated the relation between LV function and the study endpoints, 30-day cardiovascular events, and long-term cardiovascular mortality. RESULTS: Left ventricular dysfunction was diagnosed in 506 (50%) patients of which 80% were asymptomatic. In open vascular surgery (n = 649), both asymptomatic systolic and isolated diastolic LV dysfunctions were associated with 30-day cardiovascular events (odds ratios 2.3, 95% confidence interval [CI] 1.4-3.6 and 1.8, 95% CI 1.1-2.9, respectively) and long-term cardiovascular mortality (hazard ratios 4.6, 95% CI 2.4-8.5 and 3.0, 95% CI 1.5-6.0, respectively). In endovascular surgery (n = 356), only symptomatic heart failure was associated with 30-day cardiovascular events (odds ratio 1.8, 95% CI 1.1-2.9) and long-term cardiovascular mortality (hazard ratio 10.3, 95% CI 5.4-19.3). CONCLUSIONS: This study demonstrated that asymptomatic LV dysfunction is predictive for 30-day and long-term cardiovascular outcome in open vascular surgery patients. These data suggest that preoperative risk stratification should include not only solely heart failure symptoms but also routine preoperative echocardiography to risk stratify open vascular surgery patients.

Bisoprolol and fluvastatin for the reduction of perioperative cardiac mortality and myocardial infarction in intermediate-risk patients undergoing noncardiovascular surgery: a randomized controlled trial (DECREASE-IV).

OBJECTIVE: This study evaluated the effectiveness and safety of beta-blockers and statins for the prevention of perioperative cardiovascular events in intermediate-risk patients undergoing noncardiovascular surgery. SUMMARY BACKGROUND DATA: Beta-blockers and statins reduce perioperative cardiac events in high-risk patients undergoing vascular surgery by restoring the myocardial oxygen supply/demand balance and/or stabilizing coronary plaques. However, their effects in intermediate-risk patients remained ill-defined. METHODS: In this randomized open-label 2 x 2 factorial design trial 1066 intermediate cardiac risk patients were assigned to bisoprolol, fluvastatin, combination treatment, or control therapy before surgery (median: 34 days). Intermediate risk was defined by an estimated risk of perioperative cardiac death and myocardial infarction (MI) of 1% to 6%, using clinical data and type of surgery. Starting dose of bisoprolol was 2.5 mg daily, titrated to a perioperative heart rate of 50 to 70 beats per minute. Fluvastatin was prescribed in a fixed dose of 80 mg. The primary end point was the composite of 30-day cardiac death and MI. This study is registered in the ISRCTN registry and has the ID number ISRCTN47637497. RESULTS: Patients randomized to bisoprolol (N = 533) had a lower incidence of perioperative cardiac death and nonfatal MI than those randomized to bisoprolol-control (2.1% vs. 6.0% events; hazard ratios: 0.34; 95% confidence intervals: 0.17-0.67; P = 0.002). Patients randomized to fluvastatin experienced a lower incidence of the end point than those randomized to fluvastatin-control therapy (3.2% vs. 4.9% events; hazard ratios: 0.65; 95% confidence intervals: 0.35-1.10), but statistical significance was not reached (P = 0.17). CONCLUSION: Bisoprolol was associated with a significant reduction of 30-day cardiac death and nonfatal MI, while fluvastatin showed a trend for improved outcome.

A clinical randomized trial to evaluate the safety of a noninvasive approach in high-risk patients undergoing major vascular surgery: the DECREASE-V Pilot Study.

OBJECTIVES: The purpose of this research was to perform a feasibility study of prophylactic coronary revascularization in patients with preoperative extensive stress-induced ischemia. BACKGROUND: Prophylactic coronary revascularization in vascular surgery patients with coronary artery disease does not improve postoperative outcome. If a beneficial effect is to be expected, then at least those with extensive coronary artery disease should benefit from this strategy. METHODS: One thousand eight hundred eighty patients were screened, and those with > or =3 risk factors underwent cardiac testing using dobutamine echocardiography (17-segment model) or stress nuclear imaging (6-wall model). Those with extensive stress-induced ischemia (> or =5 segments or > or =3 walls) were randomly assigned for additional revascularization. All received beta-blockers aiming at a heart rate of 60 to 65 beats/min, and antiplatelet therapy was continued during surgery. The end points were the composite of all-cause death or myocardial infarction at 30 days and during 1-year follow-up. RESULTS: Of 430 high-risk patients, 101 (23%) showed extensive ischemia and were randomly assigned to revascularization (n = 49) or no revascularization. Coronary angiography showed 2-vessel disease in 12 (24%), 3-vessel disease in 33 (67%), and left main in 4 (8%). Two patients died after revascularization, but before operation, because of a ruptured aneurysm. Revascularization did not improve 30-day outcome; the incidence of the composite end point was 43% versus 33% (odds ratio 1.4, 95% confidence interval 0.7 to 2.8; p = 0.30). Also, no benefit during 1-year follow-up was observed after coronary revascularization (49% vs. 44%, odds ratio 1.2, 95% confidence interval 0.7 to 2.3; p = 0.48). CONCLUSIONS: In this randomized pilot study, designed to obtain efficacy and safety estimates, preoperative coronary revascularization in high-risk patients was not associated with an improved outcome.

High-dose beta-blockers and tight heart rate control reduce myocardial ischemia and troponin T release in vascular surgery patients.

BACKGROUND: Adverse perioperative cardiac events occur frequently despite the use of beta (beta)-blockers. We examined whether higher doses of beta-blockers and tight heart rate control were associated with reduced perioperative myocardial ischemia and troponin T release and improved long-term outcome. METHODS AND RESULTS: In an observational cohort study, 272 vascular surgery patients were preoperatively screened for cardiac risk factors and beta-blocker dose. Beta-blocker dose was converted to a percentage of maximum recommended therapeutic dose. Heart rate and ischemic episodes were recorded by continuous 12-lead electrocardiography, starting 1 day before to 2 days after surgery. Serial troponin T levels were measured after surgery. All-cause mortality was noted during follow-up. Myocardial ischemia was detected in 85 of 272 (31%) patients and troponin T release in 44 of 272 (16.2%). Long-term mortality occurred in 66 of 272 (24.2%) patients. In multivariate analysis, higher beta-blocker doses (per 10% increase) were significantly associated with a lower incidence of myocardial ischemia (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.51 to 0.75), troponin T release (HR, 0.63; 95% CI, 0.49 to 0.80), and long-term mortality (HR, 0.86; 95% CI, 0.76 to 0.97). Higher heart rates during electrocardiographic monitoring (per 10-bpm increase) were significantly associated with an increased incidence of myocardial ischemia (HR, 2.49; 95% CI, 1.79 to 3.48), troponin T release (HR, 1.53; 95% CI, 1.16 to 2.03), and long-term mortality (HR, 1.42; 95% CI, 1.14 to 1.76). CONCLUSIONS: This study showed that higher doses of beta-blockers and tight heart rate control are associated with reduced perioperative myocardial ischemia and troponin T release and improved long-term outcome in vascular surgery patients.

Perioperative cardiovascular mortality in noncardiac surgery: validation of the Lee cardiac risk index.

PURPOSE: The Lee risk index was developed to predict major cardiac complications in noncardiac surgery. We retrospectively evaluated its ability to predict cardiovascular death in the large cohort of patients who recently underwent noncardiac surgery in our institution. METHODS: The administrative database of the Erasmus MC, Rotterdam, The Netherlands, contains information on 108 593 noncardiac surgical procedures performed from 1991 to 2000. The Lee index assigns 1 point to each of the following characteristics: high-risk surgery, ischemic heart disease, heart failure, cerebrovascular disease, renal insufficiency, and diabetes mellitus. We retrospectively used available information in our database to adapt the Lee index calculated the adapted index for each procedure, and analyzed its relation to cardiovascular death. RESULTS: A total of 1877 patients (1.7%) died perioperatively, including 543 (0.5%) classified as cardiovascular death. The cardiovascular death rates were 0.3% (255/75 352) for Lee Class 1, 0.7% (196/28 892) for Class 2, 1.7% (57/3380) for Class 3, and 3.6% (35/969) for Class 4. The corresponding odds ratios were 1 (reference), 2.0, 5.1, and 11.0, with no overlap for the 95% confidence interval of each class. The C statistic for the prediction of cardiovascular mortality using the Lee index was 0.63. If age and more detailed information regarding the type of surgery was retrospectively added, the C statistic in this exploratory analysis improved to 0.85. CONCLUSION: The adapted Lee index was predictive of cardiovascular mortality in our administrative database, but its simple classification of surgical procedures as high-risk versus not high-risk seems suboptimal. Nevertheless, if the goal is to compare outcomes across hospitals or regions using administrative data, the use of the adapted Lee index, as augmented by age and more detailed classification of type of surgery, is a promising option worthy of prospective testing.

Effects of cardiopulmonary bypass on sufentanil pharmacokinetics in patients undergoing coronary artery bypass surgery.

BACKGROUND: Complete pharmacokinetic modeling, including assessment of the effect of cardiopulmonary bypass (CPB) on sufentanil disposition, has not been reported. The aims of this investigation were to define a model that accurately predicted sufentanil concentrations during and after cardiac surgery and to determine if CPB had a clinically significant impact on sufentanil pharmacokinetics. METHODS: Population pharmacokinetic modeling was applied to data from 21 patients undergoing coronary artery bypass grafting. The predictive ability of models was assessed by calculating bias, accuracy, and measured:predicted concentration ratios versus time. A simple three-compartment model, without covariates, was initially compared with models having weight or gender as covariates and was subsequently used as the foundation for multiple CPB-adjusted models (allowing step-changes of parameters at the start or end of CPB). The primary criterion for choosing more complex models was a significant improvement in log-likelihood; secondary criteria were significant improvement in bias or accuracy. RESULTS: Neither covariate (weight or gender) models improved bias or accuracy compared with the simple three-compartment model. A final CPB-adjusted model with V2 and Cl3 changing at the start of CPB and V1, Cl2, and Cl3 changing at the end of CPB had significantly greater log-likelihood values when compared with the simple three-compartment model and with less elaborate CPB-adjusted models. However, bias and accuracy for this final model were not significantly different from the simple three-compartment model. CONCLUSIONS: When sufentanil is infused at a constant rate, with initiation of CPB, a pharmacokinetic model adjusted for CPB predicts that the sufentanil concentration will decrease approximately 17% and that it will begin to return to the prebypass concentration 12 min after initiation of CPB. At the end of CPB, this model also predicts a brief spike of the sufentanil concentration. These predictions reflect changes in the measured sufentanil concentrations. However, compared with a simple, three-compartment model, incorporating step-changes of pharmacokinetic parameters at the start or end of cardiopulmonary bypass (or both) did not significantly improve overall perioperative prediction of measured sufentanil concentrations. This suggests that CPB has clinically insignificant effects on sufentanil kinetics in adults.

Aortic stenosis: an underestimated risk factor for perioperative complications in patients undergoing noncardiac surgery.

PURPOSE: To determine the incidence of perioperative events in patients with aortic stenosis undergoing noncardiac surgery. METHODS: We studied 108 patients with moderate (mean gradient, 25 to 49 mm Hg) or severe (mean gradient, > or =50 mm Hg) aortic stenosis and 216 controls who underwent noncardiac surgery between 1991 and 2000 at Erasmus Medical Center. Controls were selected based on calendar year and type of surgery. Details of clinical risk factors, type of surgery, and perioperative management were retrieved from medical records. The main outcome measure was the composite of perioperative mortality and nonfatal myocardial infarction. RESULTS: There was a significantly higher incidence of the composite endpoint in patients with aortic stenosis than in patients without aortic stenosis (14% [15/108] vs. 2% [4/216], P <0.001). This rate of perioperative complications was also substantially higher in patients with severe aortic stenosis compared with patients with moderate aortic stenosis (31% [5/16] vs. 11% [10/92], P = 0.04). After adjusting for cardiac risk factors, aortic stenosis remained a strong predictor of the composite endpoint (odds ratio = 5.2; 95% confidence interval: 1.6 to 17.0). CONCLUSION: Aortic stenosis is a risk factor for perioperative mortality and nonfatal myocardial infarction, and the severity of aortic stenosis is highly predictive of these complications.

Optimizing long-term cardiac management after major vascular surgery: Role of beta-blocker therapy, clinical characteristics, and dobutamine stress echocardiography to optimize long-term cardiac management after major vascular surgery.

BACKGROUND: Survivors of major vascular surgery are at increased risk of late cardiac complications. OBJECTIVE: To examine the cardioprotective effect of beta-blockers. METHODS: A follow-up study was conducted in 1286 patients who survived surgery for at least 30 days. Patients were screened for cardiac risk factors and dobutamine stress echocardiography (DSE) results; 1034 patients (80%) underwent preoperative DSE, and 370 (29%) received beta-blockers. The main outcome measure was late cardiac death or myocardial infarction. RESULTS: Seventy-four patients (5.8%) had late cardiac events. Cardiac event rates in patients with 0, 1 to 2, and 3 or more risk factors were 1.6%, 4.7%, and 19.2%, respectively. In patients without risk factors, beta-blockers were associated with improved event-free survival (2.8% vs 0%), and DSE had no additional prognostic value. In patients with 1 to 2 risk factors, the presence of ischemia during DSE increased cardiac events from 3.9% to 9.8%. However, if patients with ischemia were treated with beta-blockers, the risk decreased to 7.2%. In patients with 3 or more risk factors, DSE and beta-blockers stratified patients into intermediate- and high-risk groups. In patients without ischemia, beta-blockers reduced the cardiac event rate from 15.1% to 9.5%, whereas the cardioprotective effect was limited in patients with 3 or more risk factors and positive DSE findings. CONCLUSIONS: Long-term beta-blocker use is associated with a reduction in the cardiac event rate, except for patients with 3 or more risk factors and positive findings on DSE.

Cardiopulmonary bypass has minimal effects on the pharmacokinetics of fentanyl in adults.

BACKGROUND: Although fentanyl has been widely used in cardiac anesthesia, no complete pharmacokinetic model that has assessed the effect of cardiopulmonary bypass (CPB) and that has adequate predictive accuracy has been defined. The aims of this investigation were to determine whether CPB had a clinically significant impact on fentanyl pharmacokinetics and to determine the simplest model that accurately predicts fentanyl concentrations during cardiac surgery using CPB. METHODS: Population pharmacokinetic modeling was applied to concentration-versus-time data from 61 patients undergoing coronary artery bypass grafting using CPB. Predictive ability of models was assessed by calculating bias (prediction error), accuracy (absolute prediction error), and measured:predicted concentration ratios versus time. The predictive ability of a simple three-compartment model with no covariates was initially compared to models with premedication (lorazepam vs. clonidine), sex, or weight as covariates. This simple model was then compared to 18 CPB-adjusted models that allowed for step changes in pharmacokinetic parameters at the start and/or end of CPB. The predictive ability of the final model was assessed prospectively in a second group of 29 patients. RESULTS: None of the covariate (premedication, sex, weight) models nor any of the CPB-adjusted models significantly improved prediction error or absolute prediction error, compared to the simple three-compartment model. Thus, the simple three-compartment model was selected as the final model. Prospective assessment of this model yielded a median prediction error of +3.8%, with a median absolute prediction error of 15.8%. The model parameters were as follows: V1, 14.4 l; V2, 36.4 l; V3, 169 l; Cl1, 0.82 l. min-1; Cl2, 2.31 l x min-1; Cl3, 1.35 l x min-1. CONCLUSIONS: Compared to other factors that cause pharmacokinetic variability, the effect of CPB on fentanyl kinetics is clinically insignificant. A simple three-compartment model accurately predicts fentanyl concentrations throughout surgery using CPB.

Statins are associated with a reduced incidence of perioperative mortality in patients undergoing major noncardiac vascular surgery.

BACKGROUND: Patients undergoing major vascular surgery are at increased risk of perioperative mortality due to underlying coronary artery disease. Inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (statins) may reduce perioperative mortality through the improvement of lipid profile, but also through the stabilization of coronary plaques on the vascular wall. METHODS AND RESULTS: To evaluate the association between statin use and perioperative mortality, we performed a case-controlled study among the 2816 patients who underwent major vascular surgery from 1991 to 2000 at the Erasmus Medical Center. Case subjects were all 160 (5.8%) patients who died during the hospital stay after surgery. From the remaining patients, 2 controls were selected for each case and were stratified according to calendar year and type of surgery. For cases and controls, information was obtained regarding statin use before surgery, the presence of cardiac risk factors, and the use of other cardiovascular medication. A vascular complication during the perioperative phase was the primary cause of death in 104 (65%) case subjects. Statin therapy was significantly less common in cases than in controls (8% versus 25%; P<0.001). The adjusted odds ratio for perioperative mortality among statin users as compared with nonusers was 0.22 (95% confidence interval 0.10 to 0.47). Similar results were obtained in subgroups of patients according to the use of cardiovascular therapy and the presence of cardiac risk factors. CONCLUSIONS: This case-controlled study provides evidence that statin use reduces perioperative mortality in patients undergoing major vascular surgery.

Validation of fentanyl pharmacokinetics in patients undergoing coronary artery bypass grafting.

PURPOSE: The current emphasis on more rapid recovery and earlier tracheal extubation after cardiac surgery requires greater precision in administering opioids to reap their benefits while minimizing the duration of postoperative respiratory depression. Therefore, we aimed to define a pharmacokinetic model that accurately predicts fentanyl concentrations before, during, and after cardiopulmonary bypass (CPB) in patients undergoing coronary artery bypass grafting (CABG). METHODS: Parameters for two-compartment and three-compartment models were estimated by applying population pharmacokinetic modelling to fentanyl concentration vs time data measured in 29 patients undergoing elective, primary CABG. The ability of these models to predict fentanyl concentrations in a second series of ten patients undergoing CABG was then assessed. RESULTS: A simple, three-compartment model had excellent predictive ability, with a median prediction error (PE = ([Fentanyl]meas - [Fentanyl]pred)/[Fentanyl]pred x 100%) of -0.5%, and a median absolute PE (APE = /PE/) of 14.0%. In comparison to the two-compartment models, linear regression of measured:predicted concentration ratios indicated that the three-compartment model was free of systematic and time-related changes in bias (P < 0.05). The parameters of this three-compartment model are: V1 15.0 l, V2 20.0 l, V3 86.1 l, Cl1 1.08 L x min(-1), Cl2 4.90 L x min(-1), and Cl3 2.60 L x min(-1). CONCLUSIONS: Our pharmacokinetic model provides a rational foundation for designing fentanyl dose regimens for patients undergoing CABG. When combined with previously published information regarding intraoperative fentanyl pharmacodynamics, dose regimens that reliably achieve and maintain desired fentanyl concentrations throughout the intraoperative period can be designed to achieve specific therapeutic goals.