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Competing Interests: The authors declare no conflicts of interest.

Within the last generation, the management of patients with heart disease has been transformed by advances in drug treatments, interventions and diagnostic technologies. The management of arterial hypertension saw beta-blockers demoted from first- to third-line treatment. Recent studies suggest that the goal of treatment may have to change to lower systolic blood pressures to prevent long-term organ damage. Today less than 15% of coronary revascularizations are surgical and more than 85% are done by interventional cardiologists inserting coronary stents. Thus, managing patients on dual antiplatelet therapy has become an important issue. With new generations of coronary stents, recommendations are changing fast. In the past, decisions concerning non-cardiac surgery after acute myocardial infarction were based on the delay between infarction and non-cardiac surgery. Today, the main concern is the patient's status in respect of dual antiplatelet therapy after primary percutaneous intervention. There have been advances in the management of heart failure but new drugs (ivabradine, sacubitril/valsartan) and cardiac resynchronization are recommended only in patients with an ejection fraction below 35% on optimal medication. Heart failure remains a major perioperative risk factor. Prospective studies have shown that troponin elevations represent myocardial injury (not necessarily myocardial infarction), are mostly silent and are associated with increased 30-day mortality. Monitoring (troponin assays) for myocardial injury in non-cardiac surgery (MINS) seems increasingly justified. The treatment of MINS needs further research. Technological advances, such as intelligent, portable monitors benefit not only patients with cardiac disease but all patients who have undergone major surgery and are on the wards postoperatively., (© The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The perioperative use of beta-blockers (BBs) with the aim of decreasing perioperative adverse cardiac events has been strongly supported, especially after the publication of two small trial (McSPI and DECREASE I) that showed major benefits. However, some later trials did not confirm these benefits. The POISE trial, with 8351 patients, showed reduced primary outcomes (cardiac death, non-fatal myocardial infarction, non-fatal cardiac arrest) at the expense of significant harm, increasing all-cause and sepsis-related deaths, and doubling the incidence of stroke. These results led to revised American and European guidelines. The American guideline recommended a substantial narrowing of indication for perioperative BBs, while the European guideline remained far more liberal. Since the publication of the results of POISE, meta-analyses and new studies have been published. In this review the most recent available evidence, the changes in the guidelines and the criticism on POISE results are discussed together with reasons why recent meta-analyses may not have greater certainty. This is explained by the huge numeric influence of the POISE trial and the heterogeneity in the design of the trials on perioperative BBs. Thus all the evidence available must now be taken into consideration to develop more appropriate guidelines to minimise the risks and enhance the benefits of perioperative beta-blockade.

Statins are widely used in the prevention of atheromatous disease and its complications. While their lipid lowering effects are very important, there is increasing emphasis on the other effects of statins described as pleiotropic. These include atheromatous plaque stabilisation generally ascribed to their anti-inflammatory properties. It is increasingly clear that perioperative cardiac events relate to both haemodynamic perturbations (with imbalance between oxygen demand and oxygen supply to the myocardium), and rupture/disruption of atheromatous plaques. Thus, the effects of statins on perioperative cardiac outcome have been studied, mostly in observational studies. The majority of the studies have shown benefits of statin therapy. The reason for these reported benefits is the anti-inflammatory properties of statins in the face of the known release of such mediators during major surgery, leading to plaque disruption and major adverse cardiac events. To date there are too few randomised controlled studies to recommend the prophylactic administration of statins preoperatively, yet the cohort studies are suggestive of benefits.

Background: Acute perioperative beta-adrenergic blockade may be cardioprotective in the high-risk cardiac patient for major non-cardiac surgery. We have investigated the association between the heart rate achieved with perioperative beta-blockade and the incidence of perioperative cardiac complications., Methods: We identified eight randomized studies (1931 patients) reporting acute perioperative beta-blockade and major perioperative cardiovascular outcomes after non-cardiac surgery. The mean heart rates within the first 72 h after operation were analysed. A meta-analysis of means was conducted using a random effects model. A bivariate correlation analysis was conducted using Spearman's correlation coefficient to assess for an association between the mean postoperative heart rate and the 30 day cardiac outcomes., Results: Acute perioperative beta-blockade did not significantly reduce 30 day cardiac death [odds ratio (OR) 0.35, 95% confidence interval (CI) 0.08-1.52] or non-fatal myocardial infarction (OR 0.90, 95% CI 0.52-1.56) in the studies with adequate methodology. The mean (95% CI) heart rate was 73 (71-74) beats min(-1) in the beta-blockade group, which was significantly lower than the placebo group (mean heart rate 82, P=0.0001). There was no correlation between heart rate and 30 day cardiac complications (P=0.848). The reduction in heart rate was associated with increased drug-associated adverse events (OR 2.53, 95% CI 2.05-3.13, P<0.0001). A major limitation of this analysis may be that postoperative heart rate was not a primary outcome in any of the studies identified and the mean postoperative heart rate achieved may be too high to realize optimal cardioprotection., Conclusion: This meta-analysis cannot confirm that heart rate control with beta-adrenergic blockade is cardioprotective. A randomized controlled trial examining the effect of tight perioperative heart rate control with beta-adrenergic blockade on clinically important outcomes and adverse events is warranted.

We conducted a pharmaco-economic analysis of the prospective peri-operative studies of beta-blocker and statin administration for major elective non-cardiac surgery, using the Discovery Health claims costs for 2004. This analysis shows that acute peri-operative beta-blockade and statin therapy could result in a cost saving through a reduction in major perioperative cardiovascular complications in patients with an expected peri-operative major cardiovascular complication rate exceeding 10% following elective major non-cardiac surgery. The validity of these findings is dependent on whether the incidence of cardiovascular complications following major noncardiac surgery reported in the international literature is found to be similar in South Africa.

Peri-operative beta-blockade has been shown to reduce the incidence of postoperative cardio- vascular complications including cardiac death in high-risk non-cardiac surgical patients. However, the recent analysis by Lindenauer et al. suggests that it is inappropriate to administer beta-blockers blindly to all surgical patients. In an attempt to determine the appropriateness of peri-operative beta-blocker administration across patients with a spectrum of cardiovascular risks, we have examined studies of intermediate-risk patient groups (that is those undergoing intermediate risk surgery or those with a Lee Revised Cardiac Risk Score of < or =2). We analysed data from randomised prospective studies of the effects of acute peri-operative beta-blockade on the incidence of peri-operative myocardial ischaemia. By examining the demographics and surgical interventions in these patients, we have compared these studies with other studies of peri-operative silent myocardial ischaemia representing patients of similar risk. We thus estimated the expected long-term postoperative cardiovascular complication rate associated with myocardial ischaemia in these patients in terms of number needed to treat for ischaemia prevention and for prevention of major cardiovascular complications. Prevention of peri-operative myocardial ischaemia with acute beta-blockade in non-cardiac surgical patients with 1-2 RCRI clinical risk factors can be achieved with a number needed to treat of 10. It is not associated with a significant increase in drug associated side-effects. However, acute beta-blockade shows no real benefit in the prevention of major cardiovascular complications in intermediate risk non-vascular surgical patients with a number-needed-to-treat of 833. Vascular surgical patients undergoing intermediate-risk surgery may benefit from the protective effects of acute peri-operative beta-blockade, however, with a number-needed-to-treat of 68 it would require a randomised clinical trial of over 24,000 patients to prove their efficacy.

It is widely recommended that beta-blockade be used peri-operatively as it may reduce the incidence of postoperative cardiovascular complications including death. However, there are few data concerning the cost-effectiveness of such strategies. We have analysed the pharmacoeconomics of acute beta-blockade using data from eight prospective peri-operative studies in which patients underwent elective non-cardiac surgery, and in which the incidence of adverse side-effects of treatment, as well as clinical outcomes, have been reported. The costs of treatment were based on the NHS reference costs for 2004. From these data, the number-needed-to-treat (NNT) to prevent a major cardiovascular complication (including cardiovascular death) in high-risk patients was 18.5. This is comparable to the NNT for peri-operative statin therapy. The incremental cost of peri-operative beta-blockade (costs of drug acquisition and of treating associated adverse drug events) was 67.80 pounds sterling per patient. This results in a total cost of 1254.30 pounds sterling per peri-operative cardiovascular complication prevented. However, there is evidence that in patients at lower cardiovascular risk, beta-blockers may be potentially harmful, since their adverse effects (hypotension, bradycardia) may outweigh their potential cardioprotective effects.

We analysed the pharmaco-economics of the prospective peri-operative studies of statin administration for major elective vascular surgery, using the NHS reference costs for 2004. This analysis suggests that peri-operative statin therapy for patients undergoing vascular surgery may present the most cost-effective use of statin therapy yet described, with a number-needed-to-treat of 15 and almost 60% of the total cost of atorvastatin therapy recovered through a reduction in peri-operative adverse events.

Statin cardiovascular protection is mediated by lipid lowering and pleiotropic effects. The efficacy of statins has been established in non-surgical patients with cardiovascular disease and also more recently in non-surgical patients who sustain an acute coronary event. Peri-operative statin administration has been shown to improve both short-term and long-term cardiac outcome following non-cardiac and coronary bypass graft surgery. This cardioprotection may be independent of peri-operative haemodynamics due to a positive effect on plaque stability. Recommendations for the peri-operative statin administration are suggested. These include indications for peri-operative statin therapy, timing of administration, therapeutic targets, duration of administration, the adverse implications of peri-operative statin withdrawal, safety and cost-effectiveness.

Though ischaemia/reperfusion injury induces renin-angiotensin systemic (RAS) activation and increased heart angiotensin production, the effects of blockade of the two main angiotensin II receptors, AT1 and AT2, are not definitively established. Using a Langendorff heart preparation, effects of Valsartan 10(-7)M (AT1 receptor blocker), PD 123319 10(-7)M (AT2 receptor blocker) or both in the presence of a controlled concentration of angiotensin II (10(-8)M) in order to reproduce systemic RAS activation were studied in adult male Wistar rat hearts submitted to ischaemia/reperfusion. Ischaemia/reperfusion impaired both systolic and diastolic function through a no-reflow phenomenon. Presence of a controlled concentration of angiotensin in the perfusate, enough to produce a significant AT1-induced vasoconstriction before ischaemia, has no relevant influence on ischaemia/reperfusion injury. Only blockade of both AT1 and AT2 receptors significantly improved recovery from ischaemia; better ventricle function paralleled better perfusion. The results suggest that blockade of angiotensin II receptors is cumulative since blockade of AT1 and AT2 receptors is more effective than blockade of just one of them.

Objective: To assess the incidence of major cardiac events in critically ill patients with a high risk of cardiac complications presenting with an elevated heart rate., Design and Setting: Observational, retrospective study in a 15-bed medical/surgical Intensive Care Unit (ICU) at a university hospital for a period of 12 months., Patients: We studied patients with a high risk of cardiac complications, according to the revised Goldman index, who were treated for at least 36 hrs in the ICU. Patients presenting with prolonged elevated heart rate, defined as a heart rate >95 beats/min for >12 hrs in at least one 24-hr period of their ICU stay, were investigated. Cardiac high-risk patients not developing this criterion served as controls. Major cardiac events, defined as nonfatal myocardial infarction, nonfatal cardiac arrest, and cardiac related death, were the primary outcome measures., Results: From a total of 791 patients, 69 patients were assessed as cardiac high-risk patients. Of 39 patients with prolonged elevated heart rates, 19 (49%) sustained major cardiac events, whereas in the control group of 30 patients, only four patients (13%) had a major cardiac event (p = .002; odds ratio, 6.2). Patients with elevated heart rate had to be treated 4.5 days longer in the ICU (p = .01), whereas the ICU and 30-day post-ICU discharge survival rates did not differ significantly., Conclusions: In this study, we provide evidence for an increased incidence of major cardiac events in critically ill, cardiac high-risk patients with a prolonged elevated heart rate during their ICU stay. In addition, elevated heart rate was associated with a significantly longer ICU stay.

Little is known about the effect of chronic beta-adrenoceptor antagonist therapy during the peri-operative period in patients undergoing non-cardiac surgery. We conducted a literature review to identify studies examining the relationship between chronic therapy and adverse peri-operative outcome. Eighteen studies were identified in which it was possible to ascertain the incidence of adverse cardiac outcomes in those patients who were and were not receiving chronic beta-blocker therapy. None of the studies demonstrated a protective effect of chronic beta-blockade. The results of these studies were then combined and a cumulative odds ratio calculated for the likelihood of myocardial infarction, cardiac death and major cardiac complications. Patients receiving chronic beta-blocker therapy were more likely to suffer a myocardial infarction (p < 0.05). These findings differ from the published effects of acute beta-blockade. Reasons for this discrepancy are considered.

The evidence for an association between hypertensive disease, elevated admission arterial pressure, and perioperative cardiac outcome is reviewed. A systematic review and meta-analysis of 30 observational studies demonstrated an odds ratio for the association between hypertensive disease and perioperative cardiac outcomes of 1.35 (1.17-1.56). This association is statistically but not clinically significant. There is little evidence for an association between admission arterial pressures of less than 180 mm Hg systolic or 110 mm Hg diastolic and perioperative complications. The position is less clear in patients with admission arterial pressures above this level. Such patients are more prone to perioperative ischaemia, arrhythmias, and cardiovascular lability, but there is no clear evidence that deferring anaesthesia and surgery in such patients reduces perioperative risk. We recommend that anaesthesia and surgery should not be cancelled on the grounds of elevated preoperative arterial pressure. The intraoperative arterial pressure should be maintained within 20% of the best estimate of preoperative arterial pressure, especially in patients with markedly elevated preoperative pressures. As a result, attention should be paid to the presence of target organ damage, such as coronary artery disease, and this should be taken into account in preoperative risk evaluation. The anaesthetist should be aware of the potential errors in arterial pressure measurements and the impact of white coat hypertension on them. A number of measurements of arterial pressure, obtained by competent staff (ideally nursing staff), may be required to obtain an estimate of the "true" preoperative arterial pressure.

Purpose: The aim of this review of the literature was to evaluate the effectiveness of anesthetics in protecting the heart against myocardial ischemia-reperfusion injury., Source: Articles were obtained from the Medline database (1980-, search terms included heart, myocardium, coronary, ischemia, reperfusion injury, infarction, stunning, halothane, enflurane, desflurane, isoflurane, sevoflurane, opioid, morphine, fentanyl, alfentanil sufentanil, pentazocine, buprenorphine, barbiturate, thiopental, ketamine, propofol, preconditioning, neutrophil adhesion, free radical, antioxidant and calcium)., Principal Findings: Protection by volatile anesthetics, morphine and propofol is relatively well investigated. It is generally agreed that these agents reduce the myocardial damage caused by ischemia and reperfusion. Other anesthetics which are often used in clinical practice, such as fentanyl, ketamine, barbiturates and benzodiazepines have been much less studied, and their potential as cardioprotectors is currently unknown. There are some proposed mechanisms for protection by anesthetic agents: ischemic preconditioning-like effect, interference in the neutrophil/platelet-endothelium interaction, blockade of Ca2+ overload to the cytosolic space and antioxidant-like effect. Different anesthetics appear to have different mechanisms by which protection is exerted. Clinical applicability of anesthetic agent-induced protection has yet to be explored., Conclusion: There is increasing evidence of anesthetic agent-induced protection. At present, isoflurane, sevoflurane and morphine appear to be most promising as preconditioning-inducing agents. After the onset of ischemia, propofol could be selected to reduce ischemia-reperfusion injury. Future clinical application depends on the full elucidation of the underlying mechanisms and on clinical outcome trials.

Volatile anaesthetics can pharmacologically enhance the recovery of stunned myocardium, but the mechanism is still unknown. This study sought to determine whether isoflurane attenuates myocardial stunning, and whether the myocardial protection of isoflurane is mediated by adenosine A(1) receptors. Five groups (n=8) of isolated rat hearts were studied in the Langendorff apparatus. The control groups underwent 20-min ischaemia with or without adenosine receptor antagonist (DPCPX, A(1)()selective) treatment (Cont group and DPCPX group). In the isoflurane groups, isoflurane (1.5 MAC) was present throughout the experiment (Iso group) and DPCPX (200 nM) was administered from 10 min before ischaemia (Iso+DPCPX(pre-I) group) or the beginning of reperfusion (Iso+DPCPX(post-I) group) to the end of experiment. The isoflurane groups had a lower end-diastolic pressure than the control groups (P<0.05). Developed pressure recovered to 77, 76, and 82% in Iso, Iso+DPCPX(pre-I) and Iso+DPCPX(post-I) groups, respectively (P<0.05 compared with control groups). LV+dp/dt(max) recovered to 53, 86, 81, 84, and 60% of pre-ischaemic values in Cont, Iso, Iso+DPCPX(pre-I), Iso+DPCPX(post-I), and DPCPX groups. LV-dp/dt(min) recovered to 55, 84, 83, 81, and 62%, respectively. Both LV+dp/dt(max) and LV-dp/dt(min) were significantly different (P<0.05) between control and isoflurane groups during reperfusion. There were no significant differences among the isoflurane groups. Our data show that isoflurane enhances the post-ischaemic functional recovery of isolated rat heart and that block of A(1) receptors does not abolish the beneficial effects of isoflurane. We conclude that A(1)()receptors are not involved in isoflurane-induced myocardial protection in the isolated rat heart.

Two hundred and seventy-five non-cardiac surgical patients were recruited to determine risk factors associated with the development of postoperative cardiovascular complications during the first year after surgery. Patients underwent ambulatory electrocardiography pre- and postoperatively. There were 34 adverse events over the whole study period. Twenty-four occurred within 6 months and the remaining 10 occurred between 6 and 12 months postoperatively. Silent myocardial ischaemia was associated with adverse outcome over both the first 6 months [OR 4.44 (95% CI 1.77-11.13)] and the whole study period [OR 2.81 (1.26-6.07)]. Other risk factors were: vascular surgery [OR 17.09 (2.67-351.44)], history of angina [OR 6.29 (2.21-17.62)], concurrent treatment with calcium entry blockers [OR 2.68 (1.03-6.93)] and smoking [OR 4.93 (2.00-12.02)]. None of these was a useful predictor of long-term outcome (between 6 and 12 months postsurgery). These results are at variance with other published data, but we conclude that monitoring for peri-operative silent myocardial ischaemia does not aid the prediction of long-term cardiovascular complications.

Background: Both mitochondrial adenosine triphosphate-sensitive potassium (MKATP) channels (selectively blocked by 5-hydroxydecanoate) and stretch-activated channels (blocked by gadolinium) have been involved in the mechanism of ischemic preconditioning. Isoflurane can reproduce the protection afforded by ischemic preconditioning. We sought to determine whether isoflurane-induced preconditioning may involve MKATP and stretch-activated channels., Methods: Anesthetized open-chest rabbits underwent 30 min of coronary occlusion followed by 3 h of reperfusion. Before this, rabbits were randomized into one of six groups and underwent a treatment period consisting of either no intervention for 40 min (control group; n = 9) or 15 min of isoflurane inhalation (1.1% end tidal) followed by a 15-min washout period (isoflurane group; n = 9). The two groups received an intravenous bolus dose of either 5-hydroxydecanoate (5 mg/kg) or gadolinium (40 micromol/kg) before coronary occlusion and reperfusion (5-hydroxydecanoate, n = 9; gadolinium, n = 7). Two additional groups received 5-hydroxydecanoate or gadolinium before isoflurane exposure (isoflurane-5-hydroxydecanoate, n = 10; isoflurane-gadolinium, n = 8). Area at risk and infarct size were assessed by blue dye injection and tetrazolium chloride staining., Results: Area at risk was comparable among the six groups (29 +/- 7, 30 +/- 5, 27 +/- 6, 35 +/- 7, 31 +/- 7, and 27 +/- 4% of the left ventricle in the control, isoflurane, isoflurane-5-hydroxydecanoate, 5-hydroxydecanoate, isoflurane-gadolinium, and gadolinium groups, respectively). Infarct size averaged 60 +/- 20% (SD) in untreated controls versus 54 +/- 27 and 65 +/- 15% of the risk zone in 5-hydroxydecanoate- and gadolinium-treated controls (P = nonsignificant). In contrast, infarct size in the isoflurane group was significantly reduced to 26 +/- 11% of the risk zone (P < 0.05 vs.control). Both 5-hydroxydecanoate and gadolinium prevented this attenuation: infarct size averaged 68 +/- 23 and 56 +/- 21% of risk zone in the isoflurane-5-hydroxydecanoate and isoflurane-gadolinium groups, respectively (P = nonsignificant vs.control)., Conclusion: 5-Hydroxydecanoate and gadolinium inhibited pharmacologic preconditioning by isoflurane. This result suggests that MKATP channels and mechanogated channels are probably involved in this protective mechanism.

An IBM PC-based real-time data acquisition, monitoring and analysis system for experimental haemodynamic studies was developed. Comprehensive haemodynamic signals, such as aortic and left ventricular pressures, aortic and coronary blood flows, two segmental lengths, two segmental thicknesses, electrocardiogram and airway pressure, were acquired and monitored to assess cardiac function. The system performs computer-aided analysis and derivations on a number of haemodynamic parameters and cardiac function indices. The system has been tested and validated extensively over a number of series of experimental haemodynamic studies to investigate the effects of anaesthetic agents, cardiovascular drugs, and changes in loading on normal and critically ischaemic myocardium of anaesthetised laboratory subjects. Without this specialised and automated system, the analysis of the data acquired from the haemodynamic studies would be too time-consuming and could not be fully performed.

Langendorff rat hearts were used (i) to examine whether fentanyl reduces stunning, infarction or both, and (ii) to investigate if this protection is mediated by delta-opioid receptors and/or protein kinase C (PKC). In the stunning study, hearts were subjected to global ischaemia (20 min) and reperfusion. This did not produce infarction. Postischaemic mechanical function was measured in hearts treated with or without fentanyl (740 nM). Fentanyl did not affect postischaemic mechanical function. In the infarction study, the left anterior descending coronary artery was occluded for 35 min and infarct size was assessed by triphenyltetrazolium chloride staining. Hearts in the control group exhibited an infarct zone/area at risk (I/R) of 39 (SEM 5)%, whereas the I/R for the fentanyl group was 13 (2)%. When the hearts were treated with a delta-opioid receptor antagonist (naltrindole 1 nM) or a PKC inhibitor (chelerythrine 2 microM), the effect of fentanyl was abolished, with I/R of 37 (1) and 36 (2)% respectively. In our model, we conclude that fentanyl protects against infarction but not against stunning, and that the limitation of ischaemic injury is mediated by both delta-opioid receptors and PKC.

We have investigated if fentanyl protects against myocardial ischaemic injury and if so, if the mechanism of this protection is mediated via opioid and adenosine A1 receptors, and KATP channels. Langendorff rat hearts were subjected to global ischaemia (30 min) and reperfusion (60 min). The drugs were administered before induction of ischaemia and maintained throughout the experiment. Treatment with fentanyl 740 nmol litre-1 improved post-ischaemic mechanical function, assessed as developed pressure, +dP/dtmax and -dP/dtmin, compared with controls after 60 min of reperfusion. These effects were abolished by naloxone 1 mumol litre-1, DPCPX 10 mumol litre-1, a selective adenosine A1 antagonist and sodium 5-hydroxydecanoate 100 mumol litre-1, a K+ATP channel blocker. We conclude that fentanyl protected the heart against post-ischaemic injury by a mechanism which was blocked by an opioid and an adenosine A1 receptor antagonist and also by a KATP channel antagonist.

Background: Previous work showed a twofold increase in stiffness of nonischemic myocardium at the base during ischemia of the left anterior wall. Whether the diastolic response of nonischemic myocardium to remote ischemia depends on the localization of the ischemic or the nonischemic area is unknown., Methods: In dogs with open chests, regional function in ischemic and nonischemic myocardium was assessed (sonomicrometry) before and 5 min after occlusion of the left anterior descending coronary artery (LAD; n = 7) or the left circumflex coronary artery (LCX; n = 7)., Results: In nonischemic myocardium at the base, left anterior descending and left circumflex coronary artery occlusion both resulted in a twofold increase in chamber stiffness, whereas contractility and peak lengthening rate remained unchanged. In nonischemic myocardium of the posterior wall, left anterior descending coronary artery occlusion resulted in a significant (P<0.05 vs. control, P<0.05 vs. base) increase (mean+/-SD) in chamber stiffness (25+/-6%), contractility (17+/-5%), and peak lengthening rate (28+/-6%). In nonischemic myocardium at the apex, left circumflex coronary artery occlusion resulted in a significant (P<0.05 vs. control, P<0.05 vs. base) increase in chamber stiffness (15+/-5%), contractility (16+/-4%), and peak lengthening rate (19+/-6%)., Conclusions: Stiffening of remote nonischemic myocardium occurs regardless of the localization of the ischemic and nonischemic area. The systolic and diastolic responses of nonischemic myocardium are not necessarily homogenous but may vary among different regions.

This study was designed to examine the effect of volume loading on haemodynamic responses and regional cardiac function in dogs subjected to two infusion rates of propofol. Instrumentation was established to measure aortic and left ventricular pressures, cardiac output and myocardial segmental lengths. Measurements were taken during two successive infusion rates of propofol: 0.2 (P0.2) and 0.4 (P0.4) mg kg-1 min-1. One group (VL +) (n = 6) received volume loading (dextran 40, 10 mL kg-1 h-1), the other group (VL-) (n = 6) received only basal perfusion (Ringer solution, 2 mL kg-1.h-1). Regional blood flows were measured by radio-labelled microspheres. P0.4 induced a decrease in cardiac output and in dP/dtmax. End-diastolic length decreased with propofol without any difference between groups. Regional contractility was not modified by propofol or by volume loading. P0.4 decreased endocardial and epicardial blood flow in the VL-group only. Renal, small intestine and large intestine blood flows decreased in both groups with P0.4. P0.2 did not alter regional blood flows significantly. It was concluded that in this model, propofol infusion at 0.4 mg kg-1 min-1 induced splanchnic, renal and myocardial hypoperfusion in animals not submitted to a mild fluid loading. Fluid loading allowed myocardial perfusion to be maintained but could not prevent a marked decrease in splanchnic and renal perfusion.

One hundred and twenty-seven patients undergoing major lower limb joint replacement surgery were studied to determine the incidence of silent myocardial ischemia and to ascertain any link between pre-operative cardiac risk factors, silent myocardial ischaemia and postoperative morbidity. Patients underwent ambulatory ECG monitoring for 4 days (on the pre-operative night and for 3 days postoperatively). Postoperative cardiorespiratory symptomatology and morbidity was assessed by questionnaire at 3 months. Eighty-seven patients had risk factors for silent myocardial ischaemia; 42 patients (30 with risk factors) had peri-operative silent myocardial ischaemia. The median ischaemic loads (range) were 1.04 (0.32-13.31) min.h-1 pre-operatively and 5.53 (0.26-56.39), 6.69 (0.04-42.71) and 1.23 (0.1-53.74) min.h-1 on postoperative days 1-3, respectively. Risk factors did not predict the occurrence of silent myocardial ischaemia or an increased ischaemic load pre-operatively or overall postoperatively. New symptoms (chest pain, palpitations, breathlessness or fatigue) were associated with both silent myocardial ischaemia and ischaemic load (p < 0.05). Thus cardiac risk factors do not predict the occurrence of silent myocardial ischaemia or adverse outcome. Peri-operative silent myocardial ischaemia was associated with increased postoperative fatigue.

Nonischemic end-systolic performance decreases during ischemia. These changes in performance are likely to be dependent on the size and site of the ischemic zone, as well as the prevailing loading conditions. This study was designed to examine the effect of regional and generalized changes in inotropy on nonischemic end-systolic performance, independent of the ischemic zone size. Twenty dogs were instrumented with sonomicrometers and micromanometer pressure gauges. End-systolic pressure-thickness relationship data were obained during vena-caval balloon inflation. Measurements were obtained before and 90 s after left circumflex (LC) artery occlusion. Then, simultaneous with the occlusion of the LC artery, isoproterenol (0.04 microg/ml) was infused into the left anterior descending artery. After recovery, the same protocol was repeated before and after propranolol (0.5 mg/kg). In a separate set of animals, the same measurements were made following 2.5 and 5 microg/kg/min dobutamine. The effect of ischemia on the nonischemic end-systolic pressure-thickness relationship was expressed as the extent to which the relationship is shifted to the left. Infusion of intracoronary isoproterenol into the perfusion bed of the nonischemic zone produced a significant increase in the slope of the end-systolic pressure-thickness relationship. During ischemia, however, the extent of leftward shift of this relationship was less than that following beta-blockade. Intravenous dobutamine resulted in a dose-dependent increase in the slope of the nonischemic end-systolic pressure thickness relationship, but the extent of leftward displacement of the relationship in response to regional ischemia was less than that following the control occlusion. The nonischemic segment is coupled with the nonfunctioning ischemic zone in such a way that it is required of the nonischemic segment to operate at decreased end-systolic thickness for any end-systolic pressure, the extent of which is to be determined, in part, by the size of the ischemic zone and the contractile state of the nonischemic myocardium. The lower the contractile state prior to coronary occlusion the greater extent of leftward shift of the pressure-thickness relationship.

The protective efficacy of halogenated anaesthetics on myocardial injury has never been compared during early reperfusion and late reperfusion in an in vivo animal model. We compared recovery of left ventricular function under isoflurane (0.5 MAC) and halothane (0.5 MAC) anaesthesia after a brief period of regional ischaemia (15 min) in acutely instrumented rabbits. Rabbits were instrumented for the measurement of regional segment length and left ventricular pressure. Rabbits receiving isoflurane showed greater recovery of systolic shortening fraction (%SS) both during early and late reperfusion compared with halothane anaesthesia. Isoflurane protected the post-ischaemic myocardium to a greater extent than halothane anaesthesia. Early recovery of contractile function may be a predictor of contractile recovery during the later stages of reperfusion.

Nicorandil, a new KATP channel opener, is used in clinical practice for anti-anginal therapy. It exhibits vasodilator properties as does the halogenated anaesthetic isoflurane. We have examined the cardiovascular effects of increasing concentrations of isoflurane after administration of nicorandil in 10 adult beagle dogs anaesthetized with thiopental and whose lungs were ventilated mechanically. During surgery, anaesthesia was maintained with 1.0-1.5% isoflurane. A left thoracotomy was performed and the heart suspended in a pericardial cradle. Monitoring included: ECG; aortic, left ventricular, arterial, central venous and pulmonary artery pressures; cardiac output; coronary flow; and segmental length in the apical region. After surgery, isoflurane anaesthesia was set at an end-tidal concentration of 1.05% (1 MAC) and measurements obtained; these were repeated with 1.4%, 1.75%, 2.1% and 1.05% isoflurane concentrations after appropriate stabilization periods. Nicorandil (100 micrograms kg-1 bolus, 25 micrograms kg-1 min-1 infusion) was begun and a second dose-response study of isoflurane was obtained as before. Blood samples were obtained for measurement of concentrations of nicorandil. Systolic ventricular function was assessed by systolic shortening (%SS) and preload recruitable stroke work (PRSW). Increasing isoflurane concentration produced decreases in heart rate, systolic pressure, cardiac output, %SS and PRSW. Nicorandil produced a slight decrease in systolic arterial pressure (10 and 15 mm Hg after 1.05% and 2.05% isoflurane) and a slight increase in heart rate (10 and 5 beat min-1 after 1.05% and 2.05% isoflurane). Preload, assessed by end-diastolic length, decreased. Coronary blood flow increased with infusion of nicorandil. Left ventricular function was not affected by infusion of nicorandil. We conclude that nicorandil has only minor vaso/venodilatory effects in the presence of isoflurane. Ventricular function was not altered by infusion of nicorandil.

Background: The intravenous anaesthetic propofol has been shown to possess free radical scavenging activity and calcium channel blocking effects in a number of in vitro models. We decided to compare the effects of propofol with those of fentanyl on myocardial contractility during and after ischaemia to determine whether propofol could protect the heart and improve recovery of ventricular contractile function in open-chested dogs., Methods: Twenty adult beagles were acutely instrumented, under halothane anaesthesia, to measure ECG; aortic, left ventricular pressures; cardiac output; coronary flow; and segmental lengths in the regions perfused by the left anterior and left circumflex coronary arteries. After surgery and a stabilisation period halothane anaesthesia was terminated and fentanyl (100 microg x kg[-1] bolus followed by 2 microg x kg[-1] x min[-1] infusion; n=10) or propofol (5 mg x kg[-1] bolus followed by 0.3 mg x kg[-1] x min[-1] infusion; n=10) anaesthesia commenced. After a stabilisation period the LAD coronary artery was occluded for 10 min and then reperfused for 3 h. Measurements were taken throughout the protocol., Results: We found no significant difference in recovery of contractile function between propofol and fentanyl as assessed by normalised preload recruitable work area (50+/-10 vs 47+/-16%), normalised systolic shortening (36+/-12 vs 48+/-14%) and peak left ventricular dP/dt (1665+/-276 vs 1846+/-151 mmHg x s[-1]) at the end of reperfusion., Conclusion: We conclude that at the concentration used in this study propofol shows no improvement in contractility during "stunning" when compared to fentanyl.

A large epidemiological data set was used to identify 115 patients who died from a cardiovascular cause within 30 days of elective surgery under general anaesthesia. For each patient, a control was identified, matched for age (within 5 yr of the patient), sex, operation and consultant. Patients and controls were compared for cardiovascular risk factors in a matched analysis using conditional logistic regression, and a prognostic model was generated. Three risk factors were included in the final model: previous myocardial infarction (odds ratio 3.18 (95% confidence intervals (CI) 1.22-8.28), P = 0.018), history of hypertension (odds ratio 1.90 (0.99-3.62), P = 0.047) and renal failure (odds ratio 3.56 (1.04-12.10), P = 0.043).