Demetrios G. Lappas's research while affiliated with Harvard Medical School and other places

The present clinical study was undertaken to assess the alterations in myocardial metabolism and coronary haemodynamics during weaning from mechanical ventilation in postoperative cardiac surgical patients. Global and regional myocardial blood flow and metabolism were assessed using a dual port coronary sinus-great cardiac vein thermodilution catheter in 17 patients who had undergone coronary revascularization and who were being weaned from mechanical ventilation. Anaerobic myocardial metabolism, as demonstrated by the production of myocardial lactate, manifested in 8 of 17 patients during at least one of the weaning phases. There were no differences in coronary blood flow between patients who produced myocardial lactate and those who maintained aerobic cardiac metabolism. However, lactate producers exhibited larger changes in systemic vascular resistance and mean arterial pressure than the non-lactate producers. This metabolic manifestation of myocardial ischaemia was not accompanied by electrocardiographic changes of ischaemia, nor presence of chest pain, and may represent another form of silent ischaemia. We conclude that despite coronary revascularization, the myocardium may remain vulnerable to ischaemic anaerobic metabolism in the immediate postoperative period.

To quantitate the importance of cardiac dysfunction as a stimulus for plasma immunoactive beta-endorphin (iBE) secretion, we measured iBE and hemodynamic indices in 65 patients prior to anesthetic induction for coronary artery bypass grafting or valve replacement. Linear regression analysis for the group as a whole showed significant correlations between iBE and stroke index (SI), pulmonary artery wedge pressure (PCW), and right atrial pressure (RAP), but not mean arterial pressure (MAP). Two patient subgroups were identified (P less than 0.001 by F-test): those with low SI and high iBE, or those with high SI and low iBE (cutoffs at 40 ml/m2 and 35 pg/ml, respectively). Correlations between hemodynamics and iBE were always stronger within the low-SI than the high-SI subgroups. These correlations were greater for patients with coronary artery than with valvular heart disease. Cardiac output (CO) and cardiac index (CI) correlated with iBE in valve-replacement and coronary-grafting groups. These findings were not an artifact of impaired iBE clearance due to renal dysfunction. Our results quantitate the importance of hemodynamic dysfunction for iBE secretion, and indicate that this relationship is particularly strong when stroke index declines below 40 ml/m2.

Global coronary blood flow and metabolism were measured in seven patients on the first postoperative day following coronary revascularization to test the hypothesis that tracheal extubation produces adverse haemodynamic responses akin to those observed during tracheal intubation. Regional coronary flow and metabolic measurements were made in five of the seven patients. Extubation from a continuous positive airway pressure (CPAP) of 5 cm H2O was associated with a statistically significant rise in cardiac index from 3.44 +/- 0.23 L.min-1.m-2 to 3.73 +/- 0.15 L.min-1.m-2 related to an increase in stroke index, without significant changes in heart rate, mean arterial and pulmonary capillary wedge pressure. Consequently the changes in myocardial oxygen consumption (8.52 +/- 0.55 to 8.85 +/- 0.93 ml.min-1) and coronary blood flow (172 +/- 18 to 179 +/- 17 ml.min-1) were less prominent than those reported during intubation, where substantial rises in myocardial oxygen consumption and coronary flow occurred. Two patients experienced cardiac lactate production but there were no changes in systemic or coronary haemodynamics, nor were there clinical or electrocardiographic signs of ischaemia. We conclude that extubation does not appear to be associated with adverse systemic or coronary haemodynamic responses in patients following coronary bypass grafting. However, the revascularized myocardium may remain vulnerable to anaerobic metabolism in the immediate postoperative period.

The dimensional changes (measured by ultrasonic miniaturized transducers) of the left ventricle (LV), and proximal aorta (PAo) that accompanied hemodynamic changes during a forty-minute period of cross-clamping of the descending thoracic aorta without (Group A, 5 dogs) or with (Group B, 5 dogs) controlled vasodilation with sodium nitroprusside (SNP) infusion were evaluated in 10 open-chest anesthetized dogs. In both groups, measurements were repeated for another thirty-minute period after declamping. In Group A, during clamping, systemic vascular resistance (SVR), PAo pressure (PAoP), LV systolic pressure (LVSP), and PAo midwall stress increased significantly (p < 0.001). LV end-diastolic pressure (LVEDP), stroke volume (SV), cardiac output (CO), and coronary blood flow (CBF) did not show major variations, whereas systolic and diastolic LV wall thickness were significantly reduced (p < 0.02). A reduction in systolic shortening and thickening was observed also (p > 0.05). In Group B, during the same period, CO and CBF increased substantially (p < 0.02). SVR, PAoP, LVEDP, PAo midwall stress, and SV remained close to baseline values, while systolic and diastolic (p < 0.05) segmental length and systolic shortening and thickening increased (p > 0.05). Furthermore, the velocity of systolic shortening in Group B was significantly higher (p < 0.005) than in Group A. In conclusion, the data indicate that significant changes, as detected continuously by sonomicrometry, in LV wall geometry and PAo midwall stress were observed during aortic cross-clamping. SNP infusion appeared to be an effective pharmacologic intervention to control these changes and to preserve cardiovascular performance.

The global and regional coronary hemodynamic and myocardial metabolic effects of isoflurane administered intraoperatively as an adjunct to sufentanil were studied in seven of nine patients who experienced increased systemic arterial pressure while undergoing elective coronary artery bypass grafting. All patients were premedicated and maintained on their preoperative medications (beta-blockers, nitrates, Ca++ entry blockers) up to and including the morning of surgery. Systemic and pulmonary hemodynamics and global (coronary sinus, CS) and regional (great cardiac vein, GCV) coronary blood flows were measured, and blood samples were obtained for systemic and myocardial metabolic parameters: after induction with 30 mcg/kg of sufentanil and 0.12 mg/kg vecuronium (FIO2 1.0), but prior to incision (control); 5 min after sternotomy; and during ventilation with isoflurane-oxygen. Heart rate, cardiac output, stroke volume, and GCV/CS flow ratio did not change throughout the study. Neither global nor regional myocardial lactate production was detected in any patient at any time, and the electrocardiogram (lead II, V5) remained unchanged. In response to sternotomy, seven of nine patients experienced an increase in mean systemic arterial pressure of 20% or more (27 +/- 3% from control values), due to an elevation in systemic vascular resistance (30 +/- 5%). Coronary sinus (CS) and great cardiac vein (GCV) flows, as well as CS and GCV lactate extractions, were unchanged 5 min after sternotomy. Both global and regional myocardial oxygen extraction increased, while coronary venous oxygen content decreased. Isoflurane was administered in a dose that restored systemic arterial pressure to baseline values (inspired concentration 0.75-1.0%).(ABSTRACT TRUNCATED AT 250 WORDS)