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Background : Recent data suggest that beta blockers are associated with increased perioperative risk in hypertensive patients. We investigated whether beta blockers were associated with an increased risk in elderly patients with raised preoperative arterial blood pressure. Methods We conducted a propensity-score-matched cohort study of primary care data from the UK Clinical Practice Research Datalink (2004–13), including 84 633 patients aged 65 yr or over. Conditional logistic regression models, including factors that were significantly associated with the outcome, were constructed for 30-day mortality after elective noncardiac surgery. The effects of beta blockers (primary outcome), renin–angiotensin system (RAS) inhibitors, calcium-channel blockers, thiazides, loop diuretics, and statins were investigated at systolic and diastolic arterial pressure thresholds. Results Beta blockers were associated with increased odds of postoperative 30-day mortality in patients with systolic hypertension (defined as systolic BP >140 mm Hg; adjusted odds ratio [aOR]: 1.92; 95% confidence interval [CI]: 1.05–3.51). After excluding patients for whom prior data suggest benefit from perioperative beta blockade (patients with prior myocardial infarction or heart failure), rather than adjusting for them, the point estimate shifted slightly (aOR: 2.06; 95% CI: 1.09–3.89). Compared with no use, statins (aOR: 0.35; 95% CI: 0.17–0.75) and thiazides (aOR: 0.28; 95% CI: 0.10–0.78) were associated with lower mortality in patients with systolic hypertension. Conclusions These data suggest that the safety of perioperative beta blockers may be influenced by preoperative blood pressure thresholds. A randomised controlled trial of beta-blocker withdrawal, in select populations, is required to identify a causal relationship.

Background There is uncertainty regarding the prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurements after noncardiac surgery. Methods The current study undertook a systematic review and meta-analysis. The study used six search strategies and included noncardiac surgery studies that provided data from a multivariable analysis assessing whether a postoperative troponin or creatine kinase muscle and brain isoenzyme measurement was an independent predictor of mortality or a major cardiovascular event. Independent investigators determined study eligibility and abstracted data in duplicate. Results Fourteen studies, enrolling 3,318 patients and 459 deaths, demonstrated that an increased troponin measurement after surgery was an independent predictor of mortality (odds ratio [OR] 3.4, 95% confidence interval [CI] 2.2-5.2), but there was substantial heterogeneity (I(2) = 56%). The independent prognostic capabilities of an increased troponin value after surgery in the 10 studies that assessed intermediate-term (≤ 12 months) mortality was an OR = 6.7 (95% CI 4.1-10.9, I(2) = 0%) and in the 4 studies that assessed long-term (more than 12 months) mortality was an OR = 1.8 (95% CI 1.4-2.3, I(2) = 0%; P < 0.001 for test of interaction). Four studies, including 1,165 patients and 202 deaths, demonstrated an independent association between an increased creatine kinase muscle and brain isoenzyme measurement after surgery and mortality (OR 2.5, 95% CI 1.5-4.0, I(2) = 4%). Conclusions An increased troponin measurement after surgery is an independent predictor of mortality, particularly within the first year; limited data suggest an increased creatine kinase muscle and brain isoenzyme measurement also predicts subsequent mortality. Monitoring troponin measurements after noncardiac surgery may allow physicians to better risk stratify and manage their patients.

Myocardial dysfunction may contribute to the haemodynamic instability which accompanies sepsis, and may result in circulatory failure. There is no association between systolic dysfunction (SD) and mortality in septic patients and there is conflicting evidence regarding the effects of diastolic dysfunction (DD) on mortality in septic patients.We conducted a systematic review and meta-analysis to investigate DD and mortality in septic patients. We included studies conducted in this patient population which investigated the association between DD reported according to tissue Doppler imaging (TDI) criteria and mortality, using the longest reported follow-up. As a secondary endpoint, we evaluated the association between SD and mortality according to the results reported by the retrieved studies.We included seven studies in our meta-analysis with 636 septic patients, 48% of them were found to have DD. We found a significant association between DD and mortality (RR 1.82, 95% CI 1.12-2.97, p = 0.02). This finding remained valid in a further analysis which including an older study reporting DD without TDI criteria. Five studies reported data on SD for a total of 581 patients, 29.6% of them with SD. No association was found between SD and mortality (RR 0.93, 95% CI 0.62-1.39, p = 0.73). Looking at subgroups, there was a trend towards higher mortality comparing isolated DD or combined SD-DD vs normal heart function (p = 0.10 and p = 0.05, respectively).Diastolic dysfunction is common in septic patients and it is associated with mortality. Systolic dysfunction is less common and is not associated with mortality in this group of patients.

Cardiovascular complications of anaesthesia and surgery remain frequent and have short- and long-term consequences. Identification of high-risk patients is an essential step in the management of patients with cardiovascular disease who are not always fully investigated before admission for non-cardiac surgery. Clinical risk indices allow the risk of complications to be evaluated. However, many indices are inadequate in vascular surgical patients, and there is a need for objective testing of cardiac function and coronary reserve, as poor left ventricular function and reversible ischaemia during stress test are predictors of increased cardiac risk. These tests allow the patient's condition to be optimized. This may include coronary bypass surgery. Recently, biological markers of left ventricular dysfunction and of myocardial damage have been introduced. Brain natriuretic peptide concentration is inversely correlated with the ejection fraction, while troponins I and T are very valuable markers of myocardial damage.

Myocardial ischaemia occurs frequently during the peri-operative period and is associated with major cardiac events in patients with silent or overt coronary artery disease. Often caused by an imbalance between excessive oxygen demand and limited oxygen supply, ischaemia may also occur as a result of endothelial dysfunction in diseased coronary arteries. Myocardial ischaemia impairs systolic and diastolic ventricular function and facilitates the development of arrhythmias. The effects of myocardial ischaemia may persist after reperfusion (myocardial stunning). When ischaemia is chronic, down-regulation of ventricular function (myocardial hibernation) allows the heart to recover after reperfusion. Peri-operatively myocardial ischaemia is most frequently silent and is caused by haemodynamic aberrations, coagulation disorders and/or hypoxaemia. Prevention of peri-operative silent ischaemia is necessary in order to reduce the risk of adverse cardiac events.

Objectives: The effects of changes in preload on paradoxical myocardial wall motion during ischemia have been previously studied. However, the studies have been performed using slow volume changes. It was decided to study the effects of fast changes in preload, which would occur during caval occlusion, on the regional pressure-length loops during ischemia. Design: Retrospective trial. Setting: Experimental animal laboratory in a university medical center. Participants: Ten anesthetized adult dogs. Interventions: In an open chest preparation, regional ischemia was achieved by occluding the left anterior descending coronary artery for 10 minutes, with sudden caval occlusions being performed to assess the influence of preload on wall motion. Measurements and Main Results: Left ventricular pressure and regional segmental lengths were measured. During caval occlusion, beat by beat, percent postsystolic shortening and percent systolic bulging in the ischemic region, percent isovolumetric shortening in the nonischemic region, and percent systolic shortening in both regions were calculated. Caval occlusion significantly decreased the end-diastolic pressure (12.62 ± 1.02 to 3.39 ± 0.59 mmHg) and length. In the ischemic area, although systolic shortening became more negative (−1.8 ± 0.79% to −9.65 ± 1.08%), postsystolic shortening (9.66 ± 0.73% to 15.53 ± 1.2%) and systolic bulging (4.6 ± 0.49% to 12.67 ± 1.04%) increased. In the nonischemic area, systolic shortening decreased slightly but significantly (18.01 ± 3.24% to 14.93 ± 3.64%) as isovolumetric shortening increased (2.77 ± 0.68 to 7.37 ± 1.29%). Caval occlusion increased the rightward shift and accentuated the distortion of the ischemic loop. The nonischemic loop displayed a leftward shift of the systolic isovolumetric component and a slight decrease in percent total length change. Conclusion: Caval occlusion modifies the shape of the pressure-length loop of the ischemic myocardium. This change in shape may interfere with the assessment of regional systolic indexes obtained by caval occlusion in ischemic hearts.

Objectives. This study sought to explore the separate and combined effects of changes in preload, afterload and contractility on the dynamics of systolic bulging. Background. The extent of ischemic systolic bulging has been shown to be mechanically disadvantageous to left ventricular pump performance. The factors that determine ischemic segmental wall motion have not been systematically studied. Methods. Fourteen beagles were instrumented with sonomicrometers, micromanometer pressure gauges and a balloon in the inferior vena cava. Regional function was evaluated before and after 90 s of proximal left circumflex coronary artery occlusion. Occlusions were repeated after increasing systolic pressure by 5 to 10 (afterload I) and 15 to 20 mm Hg (afterload II) with graded aortic occlusion during inotropic stimulation with dobutamine (2.5 and 5 μg/kg body weight per min intravenously), with simultaneous 5-μg/kg per min dobutamine infusion and afterload II and during 2.5% halothane (negative inotrope) concentration. A 20-min recovery period was allowed between each stage of the experiment so that regional function returned to its preocclusion level. Ischemic wall motion was characterized by percent systolic bulging and its peak positive systolic lengthening rate (+dL/dt). Results. Because bulging is markedly influenced by regional preload, systolic bulging was characterized over a wide range of end-diastolic lengths of the ischemic segment during caval balloon occlusion. During each intervention, a decrease in regional preload increased the extent of percent systolic bulging. This preload dependency was more pronounced with dobutamine infusions. An increase in afterload was not associated with increased percent systolic bulging at any given preload. At a predetermined preload, bulging was not appreciably altered when an increase in left ventricular systolic pressure was not associated with a change in peak positive first derivative of left ventricular pressure (+dP/dt) but was significantly worse when peak +dP/dt increased. Dobutamine caused a dose-dependent increase in percent systolic bulging and peak +dL/dt that was positively correlated with peak +dP/dt. Conclusions. By using different loading and inotropic interventions and analyzing the regional wall motion behavior over a range of regional preloads, we can conclude that preload and rate of pressure (tension) development are the principal determinants of systolic bulging. Increases in left ventricular pressure alone had a minimal effect on systolic bulging. (J Am Coll Cardiol 1997;29:846–55)

The effects of nitrous oxide on left ventricular diastolic function and its potential interactions with ischemia-induced diastolic dysfunction have not been described. Accordingly, we investigated the effects of nitrous oxide in ischemic and remote nonischemic myocardium during baseline, 90 min severe low-flow myocardial ischemia (systolic bulge), and reperfusion in 11 open-chest dogs. Anesthesia was maintained with fentanyl infusion (2 micrograms.kg-1.min-1), animals were ventilated with 60% nitrogen in oxygen, and hemodynamic variables were recorded prior to and after the replacement of nitrogen by 60% nitrous oxide. During baseline, nitrous oxide moderately increased chamber stiffness (+ 10%), myocardial stiffness (+33%), and unstressed length (+4%) and decreased the peak lengthening rate (-10%). Moreover, nitrous oxide decreased regional contractility during baseline (-12% at apex, -8% at base) as well as in nonischemic myocardium during myocardial ischemia (-9%) and reperfusion (-8%). However, nitrous oxide did not modify ischemia-induced systolic or diastolic dysfunction in ischemic myocardium during ischemia and reperfusion. Myocardial ischemia (+45%) and reperfusion (+57%) were associated with an increase in myocardial stiffness of nonischemic myocardium regardless of the anesthetic technique used. This study is the first to demonstrate that in addition to its well established negative inotropic effect, nitrous oxide affects regional diastolic function.

During and after an ischemic injury, maintenance and recovery of cardiac function may critically depend on remote nonischemic myocardium. Graded myocardial ischemia is associated with an approximately 50% increase in stiffness of nonischemic myocardium. We determined whether this increase in stiffness is unique to the ischemic period or persists during reperfusion. Ten anesthetized (isoflurane 1.0% vol/vol) open-chest dogs were instrumented to measure left ventricular pressure and dimensions (sonomicrometry) in ischemic and nonischemic myocardium. Regional chamber stiffness and myocardial stiffness were assessed using the end-diastolic pressure-length relationship which was modified by stepwise infusion and withdrawal of 200 mL of the animals' own blood during baseline, 45 min low flow ischemia (systolic bulge), and 60 min after the onset of reperfusion. In remote nonischemic myocardium, regional myocardial ischemia was associated with a significant (P < 0.05) increase in chamber stiffness (+44%) and myocardial stiffness (+48%). Sixty minutes after the onset of reperfusion, chamber stiffness (+54%, P < 0.05 versus baseline) and myocardial stiffness (+55%, P < 0.05 versus baseline) remained increased. Thus, the ischemia-induced increase in stiffness of remote nonischemic myocardium persists for at least 60 min after reperfusion.

We have determined the effects of alterations in preload on ischaemia-induced diastolic dysfunction in anaesthetized beagles instrumented to measure left ventricular pressure and regional dimensions. Low-flow regional ischaemia decreased peak lengthening rates in ischaemic (mean -26 (SEM 6) mm s-1, P0.01) and non-ischaemic (-8.6 (3.4) mm s-1, P0.05) myocardium. Peak lengthening rates and the time constant of iso-volumic relaxation (tau) were not affected by alterations in preload. Absolute values of tau failed to distinguish between ischaemia and control. The ischaemia-induced decrease in peak negative dP/dt was preload dependent and caused mainly by a concomitant decrease in peak left ventricular pressure. We conclude that indices derived from segmental lengthening are sensitive to ischaemia and insensitive to preload, in contrast with indices derived from left ventricular pressure. It remains to be determined if monitoring of early segmental lengthening will improve detection and assessment of perioperative myocardial ischaemia.

Patients with coronary artery disease are particularly at risk perioperatively, as myocardial infarction, unstable angina, severe arrhythmia and cardiac death may occur. These events are often preceded by prolonged silent myocardial ischaemia (MI). Moreover, perioperative MI predicts long-term adverse cardiac outcome. Therefore, it is logical to prevent and treat MI. However, the detection of perioperative MI is difficult because of low sensitivity of ST-segment monitoring, low specificity of echocardiography and insufficient availability of equipment for its monitoring. A pragmatic approach is described, including preoperative consideration of myocardial revascularization prior to non-cardiac surgery and perioperative administration of antianginal agents; the effects of clonidine are discussed as well. The role of anaesthetic techniques and normovolaemic haemodilution is considered. MI episodes may be prevented or their duration may be shortened by treating tachycardia, hypotension and, possibly, hypertension. The risks of MI are particularly high during the postoperative period because increased global oxygen consumption associated with recovery, ventilator weaning, shivering and pain may lead to tachycardia and increased ventricular load. These factors must be taken into account in order to prevent MI and improve postoperative cardiac outcome.

Though a sustained post-ischemic decrease in contractile function has been clearly established, post-ischemic diastolic function has not been thoroughly investigated. Accordingly, 11 anesthetized (isoflurane 1%) open-chest beagles were instrumented to measure left ventricular pressure and dimensions (circumferential length and wall thickness) in an apicoanterior area supplied by the left anterior descending coronary artery (LAD). Pressure-dimension relations were modified by stepwise infusion and withdrawal of 200 mL of the animals' own blood during baseline, 45 minutes partial occlusion of the LAD (systolic bulging), and 60 minutes after the onset of reperfusion. Stiffness constants were derived from the end-diastolic pressure-length and stress-strain relations, respectively. Myocardial ischemia was associated with significant (P < 0.05) alterations of the following parameters of diastolic function: (1) 47% increase in end-diastolic pressure; (2) 22% decrease in peak negative dP/dt; (3) 9% increase in the time constant of isovolumic relaxation (tau); (4) postcystolic contraction; (5) 6% increase in end-diastolic length and 10% decrease in end-diastolic thickness; (6) 12% increase in unstressed length (creep) and 13% decrease in unstressed thickness; (7) 51% increase in chamber stiffness and a 63% increase in myocardial stiffness; and (8) 40% decrease in the peak lengthening rate. After 60 minutes of reperfusion, only end-diastolic pressure and tau had returned to baseline values whereas systolic shortening fraction, postsystolic contraction, and end-diastolic and unstressed dimensions had only partially recovered. No recovery occurred in peak negative dP/dt, chamber stiffness, myocardial stiffness, and peak lengthening rate. Thus, both myocardial ischemia and reperfusion are associated with complex changes in global and regional left ventricular diastolic function.

We studied 325 patients undergoing elective noncardiac surgery who had preoperative ambulatory ECG monitoring performed for a duration of 5130 h (range 8-24 h; mean 15.8 h). Sixty-four subjects (20%) had one or more episodes of ST segment depression consistent with myocardial ischaemia. Of all preoperative cardiovascular variables measured, the presence of elevated arterial pressure, despite patients being maintained on long term antihypertensive therapy, was the only factor associated significantly with the presence of preoperative silent myocardial ischaemia (P0.002). This correlation was confirmed when arterial hypertension was defined in four separate ways. The incidence of silent ischaemia in these patients was 33-55%. We suggest that admission arterial pressure may therefore be a useful screening test to identify patients at risk of preoperative myocardial ischaemia.

Although calcium channel blockers may preserve function in ischemic myocardium, they may also produce myocardial depression and dysfunction in the presence of decreased coronary flow. This study was designed to examine the issue of possible protection afforded by diltiazem against ischemia-induced myocardial dysfunction during propofol anesthesia. In eight anesthetized and ventilated dogs, regional myocardial (ultrasonic crystals in both left anterior descending [LAD] and left circumflex [LC] perfusion areas) and global ventricular function were evaluated during progressively severe degrees of myocardial ischemia (LAD constriction) before and after intravenous diltiazem (150 μg/kg). As coronary flow decreased, heart rate increased, and arterial and coronary perfusion pressures, left ventricular dP dt , and cardiac output decreased. Systemic vascular resistance was unaffected. Diltiazem without coronary constriction increased heart rate, and decreased diastolic arterial pressures, left ventricular (LV) end-diastolic, coronary perfusion pressures, LV dP dt max, LAD coronary blood flow, stroke volume, and cardiac output. At all levels of coronary constriction following diltiazem, there were decreases in systolic and diastolic arterial pressures, stroke volume, cardiac output, LV dP dt , and coronary perfusion pressure. Heart rate increased at critical coronary constriction, and then remained constant relative to the prediltiazem state. The regional muscle effects of the reductions in coronary flow in the LAD perfusion territory included decreased systolic shortening and increased postsystolic shortening before and after diltiazem. Diltiazem did not alter the magnitude of the alterations in systolic or postsystolic shortening brought about by coronary constriction. No changes occurred in the LC area. In conclusion, diltiazem depressed global ventricular performance in the presence of propofol anesthesia, but did not worsen or protect regional myocardial function of the compromised LAD segment.

Objectives . This study was designed to investigate the changes in regional distensibility of the ischemic segment and of a remote nonischemic segment brought about by graded myocardial ischemia. Background . Ventricular distensibility is a major determinant of left ventricular end-diastolic pressure. The effects of graded myocardial ischemia on the regional distensibility of the ischemic area have not been studied. Moreover, there are few data on the effects of myocardial ischemia on the regional distensibility of the nonischemic myocardium. Methods . Nine anesthetized open chest mongrel dogs were fitted with instruments to measure left ventricular pressure and circumferential length (sonomicrometry) in the ischemic segment and in a nonischemic segment. The pressure-length relation was modified by stepwise infusion and withdrawal of 200 ml of each dog's own blood over 30 min in five consecutive stages of regional ischemia. Unstressed dimensions were obtained by repeated inferior vena cava occlusions. In both segments, regional distensibility was assessed at end-diastole by means of the constants of the pressure-length (chamber stiffness), the pressure-strain and the force-strain (myocardial stiffness) relations. Results . In the ischemic segment, partial and complete coronary occlusions were associated with a twofold increase in the chamber stiffness constant, the pressure-strain constant and the myocardial stiffness constant, whereas in the nonischemic segment the chamber stiffness constant, the pressure-strain constant and the myocardial stiffness constant increased by 50%. Conclusions . Regional myocardial ischemia is associated with a decrease in distensibility of both the ischemic and the remote nonischemic myocardium.

We have studied the effects of graded infusion rates of propofol (0.2-0.5 mg kg-1 min-1) on left ventricular global and regional function, in eight acutely instrumented dogs. Global function was assessed by measurement of aortic and left ventricular pressure, LV dP/dtmax, aortic blood acceleration and stroke volume. Regional function was assessed by measurement of systolic shortening and the end-systolic pressure-length relationship. The response of the coronary circulation to short periods of occlusion was also assessed. Administration of propofol significantly reduced left ventricular preload, as indicated by reductions in end-diastolic pressure and length; contractility was depressed, the depression being greater in the apex than in the base of the left ventricle. High infusion rates impaired relaxation. Regulation of coronary blood flow was not disrupted. Reductions in preload and contractility contributed to the propofol-induced hypotension. After 60 min, recovery from the greatest infusion rate was incomplete.

This study was designed to determine whether the end-systolic pressure-length relationship (ESPLR) reflects changes in regional contractility during the imposition of graded ischemia, and whether it is modified by diltiazem during propofol anesthesia. Seven beagles were anesthetized and instrumented to measure left ventricular pressure and subendocardial segment lengths (sonomicrometry) in the region of the left anterior descending (LAD) and circumflex (LC) arteries. Afterload was increased by the tightening of a snare around the descending thoracic aorta. Pressure-length loops were constructed and the slope of the ESPLR and the x-axis intercept, Lo, were calculated. Graded ischemia of the apical myocardium only was accomplished by the tightening of a micrometer-controlled snare around the LAD to produce Critical Constriction (CC), Ischemia 1 and 2 (I1, I2), and Total Occlusion (TO). In the basal LC region, LAD ischemia had no effect on either the ESPLR slope or Lo. In contrast, the ESPLR slope in the LAD area was decreased by ischemia at I1 (-40%), increased at TO (+69%), and unchanged at CC and I2, and was reduced by diltiazem at CC and I2 (-31% and -36%, respectively). The LAD ESPLR Lo was increased by ischemia by 64% and 61% at I2, and 91% and 122% at TO, before and after diltiazem, respectively. In the LC region, diltiazem decreased systolic shortening and the ESPLR slope. These results indicate that diltiazem has negative inotropic properties in both ischemic and nonischemic areas. Also, Lo is not a constant and must always be redetermined for every intervention. In the absence of ischemia, the ESPLR may be a reliable measure of myocardial contractility.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: The aim was to examine the effect of asynchrony and regional myocardial interaction on the pattern of segmental contraction and relaxation. Methods: Three models of asynchrony were produced. Firstly the left anterior descending artery was abruptly occluded for 60 s. Secondly, the same artery was gradually occluded to produce four degrees of ischaemia based on the severity of the mechanical dysfunction. Finally, asynchrony was created by infusing isoprenaline (0.04 μg·ml−1) into the left circumflex artery. Twelve anaesthetised beagles, weighing 16-21 kg, were used for the study. Results: The patterns of contraction and relaxation were characterised by analysing the phases of shortening and lengthening, the peak lengthening rate (dL/dt), and the timing from the onset of systole to minimum systolic length. A consistent pattern of shortening and lengthening was evident during all three models of asynchrony. There were reciprocal relations between the extent of isovolumetric shortening in the normal segment and in the abnormal segment, and on occasion between the extent of isovolumetric shortening in the normal segment and the extent of isovolumetric lengthening in the same segment. Normal segments that showed minimal shortening or even some lengthening during isovolumetric systole tended to shorten beyond ejection, while segments that shortened significantly during isovolumetric contraction, lengthened earlier. Despite no change in isovolumetric shortening, segments also shortened after ejection when the opposite segment lengthened in late systole and early diastole. Conclusions: The pattern of shortening and lengthening depends on the path of contraction or on its entire loading pattern throughout systole. It is also possible that during early isovolumetric systole a segment can either be unloaded or preloaded by an opposing segment.

Study objective – The aim was to investigate the effects of regional myocardial ischaemia, calcium, and verapamil on (a) the hysteresis and (b) slope and length axis intercept of the left ventricular end systolic pressure-length relationship. Design – Segment length in myocardium supplied by the left anterior descending coronary artery was measured in anaesthetised dogs using sonomic-rometry. Three levels of regional myocardial ischaemia were produced by stenosis and occlusion of the left anterior descending artery (ischaemia 1, ischaemia 2, and occlusion). A snare placed around the descending thoracic aorta was used to obtain temporary aortic occlusions. Subjects – Seven open chested mongrel dogs were used, weight 17 kg (range 16–20). Measurements and main results – After abrupt release of temporary aortic occlusions, end systolic lengths were greater than before the occlusion in the normal myocardium. This hysteresis was abolished by regional myocardial ischaemia. However, hysteresis was insensitive to calcium and verapamil. The length axis intercept of the end systolic pressure-length relationship was increased during ischaemia 2, during coronary occlusion, and after administration of verapamil; its slope was increased after coronary occlusion. Conclusions – (1) Viscoelastic properties of the myocardium make a major contribution to hysteresis of the end systolic pressure-length relationship; and (2) the length axis intercept of this relationship is not constant and its slope does not appear to be a sensitive indicator of regional myocardial contractility during regional ischaemia.

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.

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.

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 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.

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.

It is well recognized that patients undergoing peripheral vascular surgery are at risk for postoperative cardiac complications of anesthesia and surgery (1,2). This relates directly to the prevalence of coronary artery disease and/or hypertensive heart disease in such patients. However, as coronary artery disease may be asymptomatic, the preoperative assessment may fail to elicit symptoms or signs of coronary disease. Thus, postoperative complications may occur in patients in whom the absence of symptoms or signs of heart disease may have been falsely reassuring.

Over the past decade, much interest has been focused on diastolic cardiac function because of the realization that alterations of diastolic function may be early markers of coronary heart disease, hypertensive heart disease, and many cardiomyopathies. As many as 40% of patients presenting with cardiac failure may have intact systolic function, implicating diastolic dysfunction as the major cause of failure (1). In addition to ischemia, hypertrophy and pericarditis, left ventricular filling may be impaired because of right ventricular failure associated with bulging of the septum into the cavity of the left ventricle.

Platelet-activating factor might be responsible for the alterations of diastolic function observed in different disease states and these potential effects have not been studied. The effect of incremental concentrations of platelet-activating factor (to a maximum of 200 nM) was therefore examined in isolated perfused rat heart. Platelet-activating factor decreased coronary flow rate and contractility in a dose-dependent manner. Although high-dose platelet-activating factor decreased peak -dP/dt compared to baseline, this was not significant when compared to vehicle-administered control. There were no changes in the time constant of left ventricular relaxation and the chamber stiffness constant. These results do not support a major direct role of platelet-activating factor in diastolic dysfunction.

Objectives. Nonischemic contractile segmental performance was characterized by the end-systolic pressure-length and pressure-thickness relations during regional ischemia induced by proximal left anterior descending and left circumflex coronary artery occlusions. Background. The increases in shortening and thickening of the nonischemic myocardium during acute ishemia have been attributed to alterations in the regional loading conditions. However, it is uncertain to what extent ischemia affects the contractile performance of the nonischemic zone. Methods. Twenty-seven beagle dogs were instrumented with sonomicrometers and micromanometer pressure gauges. End-systolic pressure-length and pressure-thickness relation data were obtained during vena cava balloon inflation. Control data were obtained in both left anterior descending and left circumflex regions. Then, in random order, either the left anterior descending or left circumflex coronary artery was occluded for 90 s, and hemodynamic and nonischemic end-systolic pressure-length and pressure-thickness data were obtained. After a 45-min recovery period, the other artery was occluded, and the same recordings were obtained. Results. The end-systolic pressure-length relation exhibited variable degrees of rightward and downward shifts and the end-systolic pressure-thickness relation variable degrees of leftward and downward shifts. Left circumflex coronary artery occlusion was associated with a greater downward displacement (decreased slope) of the nonischemic end-systolic pressure-length relation than left anterior descending coronary artery occlusion. The baseline slope was the best predictor of the change in slope of the end-systolic pressure-length and pressure-thickness relations. The left circumflex coronary artery supplied a larger proportion of left ventricular myocardial mass than the left anterior descending coronary artery. Conclusions. Acute ischemia profoundly affects the end-systolic performance of the nonischemic segment. Furthermore, the site, and probably size, of the ischemic zone may be important determinants of nonischemic contractile performance.

EDITOR,—N Mamode and colleagues are correct when they state that studies of the risk of perioperative myocardial infarction are needed.1 Their study goes some way to meeting this need. The way in which they present their data, however, makes it difficult to draw useful conclusions. The results of tests of association (χ2 and Fisher's exact tests) are shown, but no indication is given of the relative risk associated with each risk factor, and no adjustment …

The effects of graded concentrations of halothane on left ventricular relaxation and phasic coronary blood flow (CBF) were studied in six open-chest, anesthetized dogs. Global and regional left ventricular function were measured. Besides the expected dose-dependent depression of contractility, regional shortening, and cardiac output, halothane caused significant increases in the time constant of relaxation (Trelax), and decreased and delayed the nadir of peak negative left ventricular dP/dt. Dose-dependent reductions of CBF were noted. Percentage CBF during isovolumic relaxation was significantly reduced and showed a strong inverse correlation with Trelax. Halothane appears to interfere with the inactivation process of the heart; this in turn may impede the early rise in CBF during isovolumic relaxation.

The effects of isoflurane-induced hypotension to mean aortic pressures of 70 and 55 mmHg on global and regional right and left ventricular performance (ultrasonic dimension technique) and on coronary hemodynamics (electromagnetic flow probes) were studied in 12 open-chest dogs (anesthetized and paralyzed by continuous infusions of fentanyl and pancuronium) with critical coronary artery stenoses (micrometer-controlled snares) of the right and left anterior descending coronary arteries. The stenoses reduced resting coronary blood flow by approximately 10% without affecting global or regional myocardial performance. During subsequent isoflurane administration, coronary blood flow fell markedly. In the areas supplied by the stenosed coronary arteries, segment length shortening decreased by 70% (P less than 0.01), and regional akinesis, paradoxical motion, or postsystolic shortening developed in 9 of 12 animals. In contrast, in the areas supplied by normal coronary arteries, myocardial segment length shortening decreased significantly less and did not show signs of dysfunction. In these non-ischemic areas at both concentrations of isoflurane, end diastolic and systolic dimensions were greater in the right than in the left ventricle, probably related to differences in right (unchanged) and left (reduced) ventricular afterloads. The data indicate that in the presence of coronary artery stenoses, isoflurane-induced hypotension may cause regional myocardial dysfunction suggestive of ischemia.

Summary and Conclusion A wide array of vasoactive agents is now available to the anesthesiologist for protection from and treatment of perioperative myocardial ischemia. Different anesthetic techniques have varying effects on the cardiovascular system, the coronary circulation, and myocardial contractile function. To recommend the use of vasoactive agents in the prevention or treatment of intraoperative myocardial ischemia based on their actions in unanesthetized patients or experimental models, and without considering the consequences of the anesthetic technique employed, would seem imprudent and may lead to worsening of ischemia. Finally, right ventricular physiology and pathophysiology is significantly different from left ventricular physiology, and thus, it is not surprising that treatment of acute right ventricular failure requires interventions that differ significantly from treatment of left ventricular failure.

The effects of increasing inspired halothane concentration (0.5, 1.0, 1.5, 2.0 per cent) upon left ventricular myocardium supplied by a critically narrowed coronary artery and a normal coronary artery were studied in 11 open-chested dogs. Regional ventricular function was measured by continuous recording of ventricular segment length using pairs of implanted miniature ultrasonic length detectors in the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LC) territories before and during critical stenosis of the LAD by a micrometer-controlled snare. Critical narrowing was documented by ischemic regional ventricular function (i.e., post-systolic shortening; systolic lengthening) limited to the LAD territory when FIO2 = 0 for 90 seconds. Hemodynamic variables (aortic, left atrial and left ventricular pressure, and heart rate) were measured, ECG lead II was recorded, and the first derivative of left ventricular pressure (LV dP/dt) and coronary perfusion pressure derived for each halothane concentration before and during LAD narrowing. Increasing halothane was associated with equivalent progressive depression of global ventricular function before and during LAD constriction. Prior to LAD constriction, no ischemic changes in regional function occurred. Regional ventricular function was normal during 0.5 percent halothane in the presence of LAD constriction. With increasing halothane during LAD constriction, ischemic regional ventricular function was observed in the LAD territory in eight of eleven hearts, whereas regional ventricular function remained normal in the LC territory. The epicardial ECG was recorded in three dogs and was insensitive as an indicator of ischemia, becoming abnormal only after severe ischemic changes were established. In these studies, in which heart rate remained constant, arterial blood pressure and LV dP/dt decreased, and left ventricular end-diastolic pressure increased, decrease in blood flow and oxygen delivery due to a lower perfusion pressure distal to the coronary artery narrowing appears to be primarily responsible for the observations. The authors hypothesize that clinically unapparent episodes of regional myocardial ischemia distal to narrowed coronary arteries may be an important cause of perioperative myocardial infarction.

Two types of titration curve (log PCO2vs. pH and whole blood [HCO3−] vs. pH) were obtained in anaesthetized dogs by altering F i CO2. Both plots reveal a significant progressive decrease in slope from arterial (a) to mixed venous ( v ) to coronary sinus (cs) blood. Lines drawn between corresponding points on the arterial and mixed vanous or coronary sinus curves have slopes determined by the Respiratory Exchange Ratio (R) and are called R lines. Differences in slope between arterial and venous ( v or cs) curves may be due to changes in blood flow or of delivery of CO2 to the blood. The former is indicated by constant R values at different CO2 tensions whilst the latter is a reflection of changing R values due to fluctuations in CO2 stores. The myocardium is not an important store for CO2 but CO2 has a profound effect on coronary blood flow and it is this that causes the difference in a-cs slopes. The reverse is true for skeletal muscle where the charging and discharging of CO2 stores brings about the difference in a- v slopes.

This study investigated the effect of hypoxia on global and regional myocardial function in the normal heart and in the heart with a critically constricted coronary artery. Eight dogs under halothane anesthesia were subjected to progressive degrees of hypoxia while global and segmental heart function as well as general hemodynamics were evaluated. In the control phase of the experiment, the coronary circulation was undisturbed. A decrease in the inspired oxygen fraction from 0.3 to 0.1 was associated with significant increases in the heart rate, cardiac output, left ventricular minute work and coronary blood flow, and significant decreases in systemic vascular resistance. regional myocardial function (measured by endocardial fiber shortening) did not change. In dogs with a critical constriction applied to the left anterior descending coronary artery (LAD), hypoxia significantly increased heart rate and decreased stroke volume. Indices of global myocardial function did not change, but regional function in the area supplied by constricted LAD was depressed during severe hypoxia. This study implies that measured indices of global heart function bear little relation to regional function when a compromised segment of the myocardium is subjected to hypoxia.

Hypertensive patients were monitored for myocardial ischaemia during anaesthesia and surgery with the V5 lead of a standard electrocardiograph. Myocardial ischaemia was detected in 11 of 39 untreated hypertensive patients and in four of seven receiving therapy with a diuretic, but in none of 44 receiving atenolol. Fourteen of the atenolol-treated patients were receiving the drug on a long-term basis and the remaining 30 were treated acutely only on the morning of surgery. When myocardial ischaemia was observed, it was always associated with noxious stimulation and tachycardia, but a conspicuous increase in arterial pressure was not usually present. We conclude that myocardial ischaemia is prevalent during anaesthesia in untreated hypertensive patients, and that pretreatment with atenolol, but not diuretics, provides prophylaxis.

Instruments were inserted to seven dogs under halothane anaesthesia, to measure global and regional left ventricular function. Anaesthesia was continued with fentanyl (100 micrograms kg-1 bolus, then 1.5 micrograms kg-1 min-1). Critical constriction was applied to the left anterior descending coronary artery. Control recordings were made, followed by bolus administration of verapamil 0.08, 0.16 and 0.32 mg kg-1, with recordings 10 min after each bolus. At the highest dose, verapamil decreased systemic arterial pressure, left ventricular dP/dt, stroke volume and systemic vascular resistance, and increased heart rate significantly. Coronary perfusion pressure decreased and, in the presence of critical constriction, coronary flow per beat decreased significantly. In the region with constriction, systolic shortening of myocardium decreased and post-systolic shortening increased significantly with addition of verapamil. The addition of a high dose of verapamil to fentanyl anaesthesia caused reduction in systolic function and development of early diastolic dysfunction in myocardium with critically limited blood supply.

The changes in total pressure-length loop area were compared with changes in effective shortening area, systolic lengthening area and postsystolic shortening area (defined with respect to enddiastolic and end-systolic lengths) of the pressure-length loop during myocardial ischemia in seven anesthetized dogs instrumented for measurement of left ventricular pressure and regional segmental wall motion (sonomicrometry) in the minor axis of the apical region of the left ventricle.Ischemia was induced by gradual tightening of a micrometercontrolled snare around the left anterior descending coronary artery, which supplied the apical myocardium. Data were obtained at normal flow, after critical constriction (loss of pulsatile coronary flow), mild ischemia (ischemia 1: onset of regional dysfunction, i.e., postsystolic shortening and mild hypokinesia) and moderate ischemia (ischemia 2: marked hypokinesia). At each stage, acute afterloading was performed by partially occluding the descending thoracic aorta.The pressure-length loops were analyzed in terms of four areas: total loop area, effective shortening area, postsystolic shortening area and systolic lengthening area. Total loop area decreased only when marked hypokinesia was present (176 ± 18.3 mm Hg x mm at ischemia 2 versus 245.1 ± 26.9 mm Hg × mm at ischemia 1, p < 0.05). However, effective shortening area (98.2 ± 0.8% of total loop area at baseline; 93.8 ± 2.4% at critical constriction; 76.3 ± 7.2% at ischemia 1; 51.9 ± 12.2% at ischemia 2) and postsystolic shortening area (1.8 ± 0.8% of total loop area at baseline; 5.2 ± 1.9% at critical constriction; 14.3 ± 3/4% at ischemia 1; 23.8 ± 5.1% at ischemia 2) changed significantly with each progressive stage of ischemia. Afterloading significantly decreased total loop area at all stages compared with normal loading, whereas effective shortening and postsystolic shortening areas changed only during ischemia (ischemia 1 and ischemia 2).Thus, the individual component areas of the pressure-length loop, in particular the effective shortening area, are more sensitive to ischemic changes than is the total loop area.

The effect of hypocapnia on global and regional myocardial function and coronary blood flow (CBF) was studied in dogs anesthetized with halothane before and after critical constriction of the left anterior descending (LAD) coronary artery. Coronary blood flow decreased 29% (P less than 0.05) when hypocapnia was induced in dogs with a normal LAD artery. Critical constriction reduced CBF by 42% (P less than 0.05). In the critically constricted LAD artery, hypocapnia did not reduce CBF. During hypocapnia and with a normal LAD artery, oxygen extraction by the myocardium increased 16% (P less than 0.01) and oxygen tension in the coronary sinus was reduced by 19% (P less than 0.001). After critical constriction of the LAD, hypocapnia was associated with an increase in oxygen extraction of 14% (P less than 0.01) and the coronary sinus oxygen tension was reduced by 21% (P less than 0.001). CBF of the left circumflex coronary artery (LC) increased 36% (P less than 0.05) after critical constriction to the LAD when compared with control values of the preconstriction phase. However, LC flow did not change during hypocapnia when critical stenosis had been applied to the LAD artery. Although oxygen supply (product of CBF and arterial oxygen content) to the myocardium was reduced during hypocapnia, regional myocardial function did not change from control values. Regional function was similarly maintained during hypocapnia and critical constriction of the LAD.