Myocardial ischemia revisited

Does perioperative myocardial ischemia lead to postoperative myocardial infarction? By Stephen Slogoff and Arthur S. Keats. Anesthesiology 1985; 62:107-14. Reprinted with permission. To determine if a relationship exists between perioperative myocardial ischemia (ST segment depression greater than or equal to 0.1 mV) and postoperative myocardial infarction (PMI), nonparticipating observers recorded all electrocardiographic, hemodynamic, and other events between arrival of patients in the operating room and onset of cardiopulmonary bypass during 1,023 elective coronary artery bypass operations (CABG). The roles of preoperative patient characteristics, quality of the operation limited by disease as rated by the surgeon and duration of ischemic cardiac arrest as risk factors for PMI also were quantified. Electrocardiographic ischemia occurred in 36.9% of all patients, with almost half the episodes occurring before induction of anesthesia. PMI was almost three times as frequent in patients with ischemia (6.9% vs. 2.5%) and was independent of when ischemia occurred. Ischemia was related significantly to tachycardia but not hypertension nor hypotension and was frequent in the absence of any hemodynamic abnormalities. The anesthesiologist whose patients had the highest rate of tachycardia and ischemia had the highest rate of PMI. Although neither single nor multiple preoperative patient characteristics related to PMI, suboptimal quality of operation and prolonged ischemic cardiac arrest increased the likelihood of PMI independent of the occurrence of myocardial ischemia. The authors conclude that perioperative myocardial ischemia is common in patients undergoing CABG, occurs randomly as well as in response to hemodynamic abnormalities, and is one of three independent risk factors the authors identified as related to PMI. PMI is unrelated to preoperative patient characteristics such as ejection fraction and left main coronary artery disease, and its frequency will relate primarily to perioperative management rather than patient selection.     

Myocardial oxygen utilization after reversible global ischemia

We tested in 20 sheep the hypothesis that oxygen consumption increases after reversible, global myocardial ischemia. Left ventricular oxygen consumption before and after 25 minutes of warm (37 degrees C) global ischemia was linearly related to a function (integral) of left ventricular circumferential systolic wall stress, altered by changing afterload. The relation is expressed in the two regression equations: LVO2 (preischemic) = 1.06.SSI + 16.8 (n = 129; r = 0.79); LVO2 (postischemic) = 4.35.SSI + 5.6 (n = 89; r = 0.65). The fourfold increase in slope (4.35 versus 1.06) indicates (p = 0.0001) a massive increase of oxygen consumption in postischemic, globally "stunned" myocardium. The inferences are that globally stunned myocardium causes severe impairment of oxygen utilization efficiency, and increased vulnerability to further ischemia if coronary vessels are diseased.     

Myocardial ischemia with left ventricular outflow obstruction

We report an unusual case of a 32-year old man who was treated for a hypertrophic obstructive cardiomyopathy (HOCM) with a DDD pacing with short AV delay reduction in the past. Without prior notice the patient developed ventricular fibrillation and an invasive cardiac diagnostic was performed, which revealed a myocardial bridging around of the left anterior descending artery (LAD). We suspected ischemia that could be either related to LAD artery compression or perfusion abnormalities due to AV delay reduction with related to diastolic dysfunction.     

Myocardial protection during revascularization for myocardial ischemia

Operations that reestablish flow to proximally obstructed coronary arteries are being applied with greater frequency and greater success. The long-term effects of such operations will ultimately be measured by increased longevity for patients with coronary artery disease, providing that perioperative injury is held to an absolute minimum and technical expertise is maintained at an absolute maximum. Application of myocardial protective techniques requires a knowledge of coronary and myocardial physiology. The use of nonrandomized applications of new protective techniques is strongly discouraged since such adventures provide little insight for the future. Further elucidation of the safe intervals for brief periods of ischemia in hearts with and without obstructed coronary arteries is needed, as are more refined measurements of physiologic and biochemical effects of revascularization techniques in regions of myocardium supplied by heterogeneously affected coronary arteries.     

Myocardial ischemia score as a preoperative screening method for intraoperative myocardial ischemia

Three hundred patients for abdominal surgery with risk factors of ischemic heart disease (IHD), such as hypertension, diabetes mellitus, hyperlipidemia, smoking, old age, obesity, familial history, electrocardiographic abnormality, other perivascular diseases and male, were included in this study. Patients older than forty years were included in the study. ST segment in lead II and V5 was recorded by ST trend monitor from the time of entering the operating room to the time of exit and intraoperative myocardial ischemia occurred in 58 patients (19.3%). Correlation coefficients between each risk factor of IHD and intraoperative myocardial ischemia were calculated by multiple regression analysis and myocardial ischemia score (MIS) was determined. Intraoperative myocardial ischemia increased in patients with more than 10 points of MIS by discriminant analysis and hitting ratio of MIS was 86.3%.     

Myocardial ischemia induces coronary t-PA release in the pig

BACKGROUND: Tissue-type plasminogen activator (t-PA) is the key factor in initiating endogenous fibrinolysis in the vascular compartment. Regulated release of t-PA from endothelial stores is rapidly induced by several humoral factors as well as coagulation activation products. The aim of the present study was to test the hypothesis that regional myocardial ischemia induces regulated release of t-PA in the coronary vasculature in vivo. METHODS: Healthy anesthetized (pentobarbital) pigs (n=8) were studied before and after a 10-min left anterior descending region coronary artery occlusion (LAD). Coronary fluxes of lactate, total t-PA antigen (ELISA, detecting both complex bound and free fraction) and active t-PA (functional assay detecting biological free fraction) were determined at 1, 3, 5 and 10 min of reflow. RESULTS: Coronary occlusion induced myocardial lactate production in all animals. Net coronary release of total t-PA, which was 21 ng/min during control, increased rapidly during reflow with a peak after only 1 min (136 ng/min), and returned to baseline within 3 min. Net release of active t-PA mirrored the overall net release response, but fell short of statistical significance. CONCLUSION: Data indicate a local myocardial profibrinolytic response following regional ischemia, which may serve as a prompt defence against coronary thromboembolic events.     

Myocardial protection with high-dose beta-blockade in acute myocardial ischemia.

OBJECTIVE: The risk of postoperative cardiac dysfunction is markedly increased by emergency coronary artery bypass grafting in the presence of acute myocardial ischemia. High dose beta-blockade during continuous coronary perfusion has been suggested as an alternative to conventional cardioplegia and this technique has been applied successfully in high risk patients for coronary artery bypass grafting (CABG) surgery. This study compared high dose beta-blockade with esmolol to continuous warm blood cardioplegia in a clinically oriented model of acute left ventricular (LV) ischemia and reperfusion. METHODS: Twelve dogs were subjected to 60 min of regional LV ischemia by left anterior descending branch (LAD) ligation. Cardiopulmonary bypass (CPB) and aortic crossclamp were applied after 45 min of ischemia. Thereafter, high dose beta-blockade during continuous coronary perfusion (ESMO, n = 6) or antegrade continuous warm blood cardioplegia (WBC, n = 6) were maintained for 60 min. Myocardial water content (measured from endomyocardial biopsies using a microgravimetric technique), global LV function (preload recruitable stroke work: PRSW), and regional LV function (echocardiographic wall motion score) were determined at baseline and after weaning from CPB. RESULTS: During aortic crossclamp interstitial edema formation was significantly higher in the WBC group with an average water gain of 2.2 +/- 0.49 vs. 0.76 +/- 0.12% in the ESMO group. Thereafter, edema resolved in both groups, but myocardial water gain remained significantly higher in the WBC group at 60 and 120 min post CPB (0.98 +/- 0.19 and 1.13 +/- 0.32% vs. 0.07 +/- 0.25 and 0.04 +/- 0.08%). Global LV function was significantly higher in the ESMO group at 60 and 120 min post CPB (PRSW 103 +/- 6 and 94.7 +/- 4.6% of baseline vs. 85.3 +/- 4.9 and 74.7 +/- 7.6% of baseline). However, regional LV function showed no significant difference between groups. CONCLUSIONS: High-dose beta-blockade during continuous coronary perfusion may allow the surgeon to utilize the advantages of warm heart surgery, while avoiding the interstitial edema formation and temporary cardiac dysfunction associated with continuous warm blood cardioplegia. In high risk patients such as patients with unstable angina or after failed PTCA, high-dose beta-blockade may be an applicable alternative to cardioplegic arrest.     

Myocardial ischemia reperfusion injury: from basic science to clinical bedside

Myocardial ischemia reperfusion injury contributes to adverse cardiovascular outcomes after myocardial ischemia, cardiac surgery or circulatory arrest. Primarily, no blood flow to the heart causes an imbalance between oxygen demand and supply, named ischemia (from the Greek isch, restriction; and haema, blood), resulting in damage or dysfunction of the cardiac tissue. Instinctively, early and fast restoration of blood flow has been established to be the treatment of choice to prevent further tissue injury. Indeed, the use of thrombolytic therapy or primary percutaneous coronary intervention is the most effective strategy for reducing the size of a myocardial infarct and improving the clinical outcome. Unfortunately, restoring blood flow to the ischemic myocardium, named reperfusion, can also induce injury. This phenomenon was therefore termed myocardial ischemia reperfusion injury. Subsequent studies in animal models of acute myocardial infarction suggest that myocardial ischemia reperfusion injury accounts for up to 50% of the final size of a myocardial infarct. Consequently, many researchers aim to understand the underlying molecular mechanism of myocardial ischemia reperfusion injury to find therapeutic strategies ultimately reducing the final infarct size. Despite the identification of numerous therapeutic strategies at the bench, many of them are just in the process of being translated to bedside. The current review discusses the most striking basic science findings made during the past decades that are currently under clinical evaluation, with the ultimate goal to treat patients who are suffering from myocardial ischemia reperfusion-associated tissue injury.     

Myocardial ischemia correlates with reduced fibrinolytic activity following peripheral vascular surgery

STUDY OBJECTIVES: To evaluate the relationship between perioperative ischemia and serial concentrations of D-dimer, which is a sensitive and specific marker of fibrinolytic activity. Myocardial ischemia and infarction are well-recognized complications of peripheral vascular surgery. We hypothesized that patients at increased risk of perioperative myocardial ischemia might be identified preoperatively by abnormal hemostatic indices. DESIGN: Prospective clinical outcomes study. SETTING: A 1,124-bed tertiary care medical center.Patients: 42 ASA physical status II, III, and IV patients undergoing peripheral vascular surgery. INTERVENTIONS: Serial D-dimer concentrations were measured preoperatively, and at 24 and 72 hours postoperatively. Continuous 12-lead ST-segment monitoring (Mortara Instrument, Inc., Milwaukee, WI) was performed with the acquisition of a 12-lead ECG every 20 seconds for 72 hours. MEASUREMENTS AND MAIN RESULTS: D-dimer measurements were performed in duplicate using the Dimer Gold assay (American Diagnostica, Greenwich CT). Ischemic episodes, as defined by continuous 12-lead ST-segment monitoring, occurred in 49% of patients. There were no demographic differences between ischemic and nonischemic groups. Although baseline D-dimer concentrations were not statistically significantly different between groups, patients experiencing perioperative myocardial ischemia generated significantly less D-dimer during the perioperative period (p = 0. 014). CONCLUSIONS: Patients with an impaired fibrinolytic response, as defined by reduced generation of D-dimer, experienced an increased incidence of perioperative myocardial ischemia.     

Myocardial protective effect of amiodarone in hypertrophied hearts during global ischemia

The effect of amiodarone on the ischemic-reperfusion injury was tested in an isolated working preparation, using hypertrophied rat heart at 37 degrees C. Constant filling and afterload pressures and similar heart rates were used. Hearts from spontaneously hypertensive rats (N = 78) had thirty minutes of ischemia. Each received a 12-ml injection, by aortic root infusion, of amiodarone in normal saline or of normal saline alone at 37 degrees C at the onset of ischemia. Heart rate, aortic output, coronary sinus output, atrial pressure, and aortic pressure were recorded before and after global ischemia under steady-state conditions. Dose-response studies were performed at concentrations of 0.01 to 1.0 mg/ml. At every dose administered, amiodarone was found to significantly ameliorate the deleterious effects of global ischemia. The maximal benefit of amiodarone (70 +/- 4.6% recovery of function [mean +/- standard error of the mean], p less than 0.01) was found to be 0.25 mg (0.021 mg/ml), or 0.11 mg/g wet heart weight. Improvement in survival (return of aortic output and heart rate following ischemia) with all doses of amiodarone was statistically significant (p less than 0.002). Decreased recovery of function following global ischemia when doses were greater than 0.25 mg may have been secondary to the known negative inotropic effects of the drug. The mechanisms for the protective effects of amiodarone may be coronary vasodilatation, antiarrhythmic stabilization, or inhibition of calcium flux at the slow channel.     

Myocardial ischemia during cesarean section in a patient with placental abruption

A 27-year-old woman (38 week pregnant) was admitted to an obstetric hospital with an acute severe abdominal pain. At that time, the fetal heart sound was not audible. The diagnosis of placental abruption was made and she underwent an emergency cesarean section (C/S) under general anesthesia. She had anemia which became worse in the first few hours after C/S, requiring blood transfusion. ST depression was also present in the ECG during this period. Subsequently, we found an increase in myocin light chain, but not in troponin-T. On the 2nd postoperative day, pulmonary edema appeared and DIC was suspected. We treated her with nitrates, diuretics, protease inhibitors and oxygen by mask. She was discharged on 14th postoperative day with no other complications. Cardiac echogram showed no abnormalities, but a borderline change was seen in her exercise ECG. Depression of the ST segment has been reported in C/S patients, but this does not indicate myocardial ischemia (MI) nor treatment is necessary in most cases. In our case, the diagnosis was not conclusive, but in view of the risks associated with MI, patients with placental abruption should be managed strictly as if they have MI.