John S. Ikonomidis

Results of combined pulmonary resection and cardiac operation

BACKGROUND Concomitant lesions of the heart and lung are uncommon, but when present they pose a therapeutic challenge for thoracic surgeons. A combined procedure avoids the need for a second major thoracic procedure and may improve outcomes and provide economic benefit. However, cardiopulmonary bypass may adversely affect the natural history of pulmonary malignancies. METHODS The clinical records of 30 patients were reviewed who underwent simultaneous lung resection and cardiac operations between January 1982 and July 1995. Follow-up was obtained on all 30 patients (mean follow-up, 22 months; range, 1 to 100 months). RESULTS Twenty-four patients underwent coronary artery bypass grafting in conjunction with pulmonary resection. Six patients underwent aortic (n = 4) or mitral (n = 2) valve replacement. The pulmonary resections consisted of pneumonectomy (n = 3), lobectomy (n = 14), wedge excision (n = 12), and tracheal resection (n = 1). Twenty-one patients had pathologic findings that confirmed adenocarcinoma (n = 10), squamous cell carcinoma (n = 5), small cell carcinoma (n = 2), or other malignancy (n = 4). Tumor stage of primary lung cancers was stage I, n = 12; stage II, n = 3; and stage IIIa, n = 2. Pathologic examination revealed benign disease in 9 patients. There were two operative deaths, one due to aspiration and one due to stroke. There were three late deaths, two cardiac and one of metastatic disease. Overall late survival was 85% +/- 7% and 73% +/- 16% at 1 and 5 years, respectively. Actuarial survival for patients with malignant disease was 64% at 5 years. CONCLUSIONS Simultaneous cardiac operation and lung resection was not associated with increased early or late morbidity or mortality. Cardiopulmonary bypass does not adversely affect survival in patients with malignant disease. Cardiac valve replacement can be performed safely in conjunction with pulmonary resection.

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.

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.

Which techniques of cardioplegia prevent ischemia

One hundred seven patients undergoing coronary artery bypass grafting were randomized to receive warm antegrade (n = 21), warm retrograde (n = 22), cold antegrade (n = 20), cold retrograde (n = 22), or intermittent cold antegrade (n = 22) blood cardioplegia. Myocardial oxygen consumption and lactate production, adenine nucleotides, and adenine nucleotide degradation products were measured during the operation, and creatine kinase-MB release was assessed postoperatively. Warm cardioplegia resulted in greater myocardial lactate production than cold cardioplegia (p = 0.048). Retrograde cardioplegia was associated with greater lactate production than antegrade cardioplegia (p = 0.015). Adenosine triphosphate depletion was similar among groups. However, poorly diffusible metabolites of adenosine triphosphate accumulated to the greatest extent in the intermittent cold group. Levels of hypoxanthine were highest after warm retrograde cardioplegia. Operative mortality and morbidity were low and were not different among groups. In summary, none of the five techniques of cardioplegia evaluated in this study was able to completely prevent myocardial ischemia. Anaerobic lactate production was minimized with cold cardioplegia and with antegrade cardioplegic delivery. Hypothermia may have impaired regeneration of adenosine triphosphate, however, particularly in association with inadequate or intermittent cardioplegic flow.

Loss of the Somatosensory Evoked Response as an Indicator of Reversible Cerebral Ischemia during Hypothermic, Low-flow Cardiopulmonary Bypass

We assessed somatosensory evoked response (SSER) as a monitor of cerebral protection during nonpulsatile, hypothermic cardiopulmonary bypass (CPB). In 13 dogs under CPB, extracorporeal flow rate (EFR) thresholds for loss of SSER were determined by stepwise reduction of the EFR from 2.0 to 0.25 L/min/m2 at perfusion temperatures of 35 degrees C, 30 degrees C, 25 degrees C, and 20 degrees C. Testing began at 35 degrees C in Group 1 (N = 6) and at 20 degrees C in Group 2 (N = 7). Immediately on loss of SSER (denoted as a decrease of 80% or more in the amplitude of the somatosensory evoked potentials), EFR was restored to 2.0 L/min/m. Thresholds for loss of SSER ranged between 0.75 and 0.25 L/min/m2. SSER was always restored on return of EFR to 2.0 L/min/m2; thus loss of SSER was a reversible ischemic change. Both groups had similar threshold values at 35 degrees C, but at lower temperatures, Group 1 thresholds were significantly higher than those in Group 2. Since 35 degrees C was the first test temperature for Group 1 but the last for Group 2, EFR reduction at 35 degrees C apparently caused neurophysiological changes (depletion of cortical energy reserves), which diminished subsequent tolerance to ischemia, but EFR reduction at 20 degrees C did not. Our findings show that loss of SSER warns of reversible cerebral ischemia, and support SSER monitoring as a useful measure of cerebral function during low-flow, hypothermic CPB.

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.

Extracellular calcium concentration affects susceptibility to global ischemic injury in newborn but not adult hearts

BACKGROUND Whether immaturity in calcium handling, that persists for a time after birth, could increase sensitivity to extracellular calcium and affect the development of global ischemic injury in the newborn heart is unknown. To address this, the impact of alterations in extracellular calcium concentration on newborn vs. adult development of myocardial injury due to ischemia was studied. METHODS In Study 1, hearts of 3-day-old piglets and adult pigs were perfused with 1 of 3 different calcium concentrations: control (0.13 mmol/L); intermediate (2.23 mmol/L); high (4.44 mmol/L) before normothermic ischemia. In Study 2, newborn hearts were allocated to perfusion with or without the L-calcium channel antagonist verapamil before high (4.44 mmol/L) calcium exposure, followed by normothermic ischemia. Tolerance to ischemia was assessed by determining the time to irreversible injury in all hearts, and maximal intraventricular pressures at peak injury. RESULTS In adults, altering calcium did not significantly affect tolerance to ischemia. In newborns, increasing calcium exposure resulted in significantly greater intraventricular pressures at maximal injury when compared with the control (low) calcium group (p<.05). As well, newborns exposed to high calcium had a significantly shorter time to the development of ischemic injury compared with the other groups (p<.05). Those newborn hearts pretreated with an L-calcium channel antagonist before the high calcium exposure did not exhibit this increased susceptibility to ischemic injury (p<.05). CONCLUSIONS In contrast to adults, the development of ischemic injury in the newborn heart is affected by changes in extracellular calcium, that can be modified with an L-calcium channel antagonist. This information could be used to prolong the safe preservation time of newborn donor hearts harvested for transplantation, as well as to minimize postoperative ventricular dysfunction.

Preconditioning to Improve Myocardial Protectiona

Major advances in the composition and delivery of cardioplegia have helped to reduce the morbidity and mortality associated with coronary bypass surgery. The discovery of the preconditioning response should facilitate the development of more powerful myocardial protective agents. These new agents may act to directly stimulate the preconditioning response or may act in a supplementary fashion to either augment the response or provide protection from alternate pathways. As new techniques of myocardial protection continue to be developed, the risk-to-benefit ratio of coronary bypass surgery will continue to improve. As a result of these improvements, surgeons will be able to offer surgery to an increasingly high risk patient population without increasing the morbidity or mortality currently associated with coronary bypass.