Toshizumi Shirai

Tepid antegrade and retrograde cardioplegia

To determine the optimal temperature for the combination of antegrade and retrograde cardioplegia, 42 patients undergoing coronary artery bypass grafting were randomized to receive cold (9 degrees C; n = 14), tepid (29 degrees C; n = 14), or warm (37 degrees C; n = 14) blood cardioplegia delivered continuously retrograde and intermittently antegrade. Myocardial oxygen utilization, lactate and acid metabolism, and coronary vascular resistance were measured during the operation and cardiac function was assessed postoperatively. Myocardial oxygen consumption, lactate release and acid release were greatest with warm, intermediate with tepid, and least with cold cardioplegia (p = 0.0001). However, washout of lactate and acid at the time of cross-clamp release was reduced (p = 0.022) with tepid or cold compared with warm cardioplegia. Early postoperative left ventricular function was best preserved (p = 0.01) after tepid than after cold or warm combination cardioplegia. These results suggest that tepid combination cardioplegia reduced metabolic demands but permitted immediate recovery of cardiac function. This technique may provide better myocardial protection than cold or warm combination cardioplegia.

Insulin stimulates pyruvate dehydrogenase and protects human ventricular cardiomyocytes from simulated ischemia

UNLABELLED Impaired myocardial metabolism after cardioplegic arrest results in persistent anaerobic lactate production. Insulin may protect the heart from ischemia and reperfusion by enhancing myocardial metabolic recovery. However, the stimulation of glycolysis during ischemia may be detrimental because of an accumulation of metabolic end-products. We examined the effect of insulin on quiescent human ventricular cardiomyocytes subjected to simulated cardioplegic ischemia and reperfusion. METHODS Primary cardiomyocyte cultures were established from patients undergoing corrective repair of tetralogy of Fallot. Cells were exposed to varying concentrations of glucose and insulin during 30 minutes of stabilization in 10 mL of phosphate-buffered saline solution. Ischemia was simulated by exposing the cells to a low volume (1.5 mL) of deoxygenated phosphate-buffered saline solution for 90 minutes followed by 30 minutes of simulated reperfusion in 10 mL of normoxic phosphate-buffered saline solution. Cell viability was assessed by trypan blue exclusion. The activity of mitochondrial pyruvate dehydrogenase was measured in 3 states: stabilization, ischemia, and reperfusion. In addition intracellular lactate, adenine nucleotides, extracellular lactate, pyruvate, and acid release were measured. RESULTS Higher ambient glucose concentrations resulted in greater cellular injury although insulin-treated cells displayed less injury after ischemia and reperfusion. Insulin increased the pyruvate dehydrogenase activity by 31% in cardiomyocytes and reduced extracellular lactate production by 40%. Intracellular adenosine triphosphate was improved by 75% in cells exposed to high glucose concentrations in the presence of insulin. CONCLUSIONS Insulin protected human ventricular cardiomyocytes from ischemia and reperfusion. This protection may be due to a stimulation of pyruvate dehydrogenase activity which resulted in improved aerobic metabolism.

The optimal cardioplegic temperature

Seventy-two patients undergoing coronary artery bypass grafting were randomized to receive cold (8 degrees C) antegrade or retrograde, tepid (29 degrees C) antegrade or retrograde, or warm (37 degrees C) antegrade or retrograde blood cardioplegia (n = 12 in each group). Myocardial oxygen utilization as well as lactate and acid metabolism were assessed intraoperatively and cardiac function was assessed postoperatively. Myocardial oxygen consumption and anaerobic lactate release were greatest during warm, intermediate during tepid, and least during cold cardioplegic arrest. Myocardial oxygen consumption and lactate release were underestimated during retrograde cardioplegia because of contamination of aortic root samples. Warm retrograde and tepid retrograde cardioplegia resulted in greater lactate and acid washout with reperfusion. Left ventricular stroke work indices were greater after warm antegrade and tepid antegrade cardioplegia than after cold antegrade cardioplegia, and right ventricular stroke work indices were greatest after warm antegrade cardioplegia. Warm antegrade cardioplegia increased aerobic metabolism during and after cardioplegia and preserved left and right ventricular function. Tepid antegrade cardioplegia reduced anaerobic lactate and acid release during arrest and preserved cardiac function.

RISK FACTORS FOR STROKE FOLLOWING CORONARY BYPASS SURGERY

Improvements in surgical technique and advances in myocardial protection have resulted in low rates of morbidity and mortality despite a greater incidence of high‐risk patients. Noncardiac morbidity prolongs hospital stays and increases the costs of cardiac surgery. This study examines the preoperative predictors of stroke following isolated coronary bypass surgery. The clinical records of 3910 consecutive patients who underwent isolated coronary bypass surgery at the University of Toronto were reviewed. Stepwise logistic regression identified six independent predictors of stroke following CABG (percent in parentheses) and calculated factor adjusted odds ratios (OR) for each risk factor. Triple vessel coronary artery disease was the most important predictor (1.9%, OR 5.71), followed by normothermic systemic perfusion (3.8%, OR 4.85), age > 70 years (3.2%, OR 3.88), a previous history of transient ischemic attacks or stroke prior to surgery (6.1 %, OR 3.7), peripheral vascular disease (4.7%, OR 2.77), and diabetes mellitus (2.6%, OR 2.01). The mechanism of stroke is likely different between these high‐risk groups and strategies to prevent postoperative stroke should focus on the mechanisms responsible in high‐risk patients.

Adequate distribution of warm cardioplegic solution

Seventy-five patients undergoing coronary artery bypass grafting were randomized to receive warm antegrade (N = 25), warm retrograde (N = 25), or a combination of warm antegrade and retrograde (N = 25) delivery of blood cardioplegic solution. Myocardial oxygen utilization, lactate and acid metabolism, and adenine nucleotides and their degradation products were measured during the operation and cardiac function was assessed postoperatively. Warm retrograde delivery of cardioplegic solution increased lactate and acid release during cardioplegia and reperfusion, decreased left ventricular adenosine triphosphate concentrations, and reduced the washout of adenine nucleotide degradation products from both left and right ventricles. Warm antegrade delivery of cardioplegic solution resulted in less lactate and acid release during cardioplegia but more lactate accumulated in the territory of the left anterior descending artery during the crossclamp period. Intermittent antegrade delivery of the cardioplegic solution during combination cardioplegia washed out lactate and acid, which suggested inhomogeneous delivery of the cardioplegic solution during continuous retrograde cardioplegia. Combination cardioplegia best preserved adenosine triphosphate in the left ventricle and resulted in the best postoperative left and right ventricular function. A combination of intermittent antegrade and continuous retrograde delivery of cardioplegic solution provided better myocardial protection than either antegrade or retrograde delivery of cardioplegic solution alone.

Antegrade and retrograde cardioplegia: Alternate or simultaneous?

UNLABELLED Neither antegrade nor retrograde cardioplegic protection provides homogeneous distribution, and a combination may be required to avoid anaerobic metabolism and depressed postoperative ventricular function. Tepid cardioplegia (29 degrees C) avoids the delayed recovery of cardiac function and metabolism associated with cold cardioplegia (15 degrees C) and reduces the anaerobic metabolism seen with warm (37 degrees C) cardioplegia. We compared two techniques that combine antegrade and retrograde tepid cardioplegia: alternate and simultaneous. METHODS Sixty patients undergoing elective isolated coronary artery bypass grafting were randomized to receive near continuous tepid retrograde and either intermittent antegrade cardioplegia (the alternate technique) or antegrade cardioplegia with the solution delivered concurrently through each completed vein graft (the simultaneous technique). RESULTS Myocardial lactate extraction was greater after crossclamp release following simultaneous than alternate cardioplegia. Postoperative ventricular function was better after alternate than simultaneous cardioplegia. CONCLUSION Both techniques permitted rapid postoperative recovery of myocardial metabolism and ventricular function. However, simultaneous cardioplegia was simpler and did not require deairing the aortic root between antegrade infusions.

Myocardial perfusion during warm antegrade and retrograde cardioplegia: a contrast echo study

BACKGROUND We evaluated distribution of warm antegrade and retrograde cardioplegia in patients undergoing coronary artery bypass grafting (CABG). METHODS Myocardial perfusion was evaluated pre- and post-CABG using transesophageal echocardiography with injection of sonicated albumin microbubbles (Albunex) during warm antegrade and retrograde cardioplegia. The left ventricle (LV) was evaluated in five segments and the right ventricle (RV) was evaluated in two segments. Segmental contrast enhancement was graded as absent (score = 0), suboptimal or weak (score = 1), optimal or excellent (score = 2), or excessive (score = 3). RESULTS Pre-CABG cardioplegic perfusion correlated weakly with severity of coronary artery stenoses (r = -0.331 and 0.276 for antegrade and retrograde cardioplegia, respectively). Antegrade cardioplegia administration resulted in 98% and 96% perfusion to the left ventricle pre- and post-CABG, respectively. Retrograde cardioplegic administration resulted in reduced LV perfusion, with 86% (p = 0.032 from antegrade) and 59% (p<0.001 from antegrade) pre- and post-CABG, respectively. The average LV perfusion score (mean +/- SEM) was greater with antegrade than retrograde cardioplegia both pre-CABG (1.93+/-0.04 vs. 1.53+/-0.11, p<0.001) and post-CABG (1.63+/-0.07 vs. 1.19+/-0.13, p = 0.004). RV perfusion was poor with both techniques pre-CABG, but improved significantly with antegrade cardioplegia post-CABG. CONCLUSIONS We conclude that warm antegrade cardioplegia results in better left ventricular perfusion than warm retrograde cardioplegia. Right ventricular cardioplegic perfusion was suboptimal, but the best delivery was achieved with antegrade cardioplegia after coronary bypass. We therefore recommend construction of the saphenous vein graft to the right coronary artery early in the operative procedure.

Results of Represervation of the Chordae Tendineae During Redo Mitral Valve Replacement

BACKGROUND Previous studies have shown that preservation of the chordae tendineae improves early and late postoperative left ventricular function after mitral valve replacement. This report describes the results of represervation of the chordae tendineae during redo mitral valve replacement in patients who had their chordae tendineae preserved during their initial operation. METHODS Fifty-four patients undergoing reoperative mitral valve replacement with preservation of their chordal annular attachments (chordae group) were compared with 187 patients who had redo mitral valve replacement without preservation of the chordae (nonchordae group). The interval between the initial operation and the reoperation was 8.7 +/- 4.4 years in the chordae group and 8.6 +/- 4.9 years in the nonchordae group (p = 0.315). Seventy-three patients underwent aortic valve replacement during their redo mitral valve replacement compared with 168 patients who had mitral valve replacement alone. There were 15 patients who had their chordal attachments represerved during redo double-valve replacement. RESULTS In the chordae group, intraoperative assessment revealed excellent chordal connection between the preserved papillary muscles and the mitral annulus in all patients. One patient had adhesions between the preserved chordae and the stent of the tissue valve. The chordal attachments were preserved during insertion of the second valve in all patients. The incidence of low output syndrome and operative mortality in the chordae group was 16.7% and 7.4%, respectively. In the nonchordae group, the incidence of low output syndrome was 27.3% (p = 0.112 compared with the chordae group) and the operative mortality was 13.4% (p = 0.236 compared with the chordae group). In patients with double-valve replacement, represervation of the chordae was associated with a reduction in low output syndrome (0% versus 24%; p = 0.034) and mortality (6.7% versus 15.5%; p = 0.374). CONCLUSIONS Preservation of the chordal attachments between the papillary muscles and the mitral annulus can be accomplished during reoperative mitral valve replacement. Represervation of the chordae tendineae may reduce postoperative low output syndrome, especially in high-risk patients undergoing redo double-valve replacement.

Optimal Myocardial Preconditioning in Humansa

Abstract: We developed a model of ischemia and reperfusion (I and R) in human ventricular myocytes (CM). CM injury and metabolics were studied after various interventions: endogenous preconditioning (PC) with anoxia, hypoxia, and anoxic or hypoxic supernatants; endogenous PC with or without SPT or adenosine deaminase; and exogenous adenosine PC before, during, or after I or continuously, with or without SPT. To assess the clinical implications of PC and the possible mediating effects of adenosine, patients undergoing elective coronary bypass surgery (CABG) received either a high or low dose of adenosine. Patients not receiving adenosine served as controls. Adenosine levels, high‐energy phosphate levels, and metabolic parameters were evaluated from blood samples and left ventricular biopsy samples. Our cellular model studies indicated that preconditioning conferred protection to human CM via an adenosine‐mediated pathway. Adenosine simulated PC without a fall in ATP. Adenosine administered to patients during CABG stimulated myocardial metabolism while preventing the degradation of high energy phosphates. A prospective randomized trial of adenosine administered to high‐risk patients for myocardial protection is required.

Myocardial protective techniques used at the University of Toronto for coronary artery bypass surgery: Past, present and future

Abstract Coronary artery bypass grafting (CABG) using a variety of myocardial preservation techniques yields excellent results. In recent years the proportion of “high risk” patient referrals has increased. Although intermittent cold blood cardioplegia with a terminal “hot shot” remains the most commonly used protective strategy at The Toronto Hospital, improved techniques of myocardial protection are being developed to resuscitate the ischaemic myocardium and to reduce operative complications in this changing patient population requiring surgical revascularisation. Many controversies in the development of these myocardial protective strategies still remain. New developments which may be implemented in the future to improve operative results include refinement of myocardial temperature control, ischaemic “preconditioning”, and the use of adenosine analogues as cardioplegic additives.