John H. Siegel

Detection of creatine kinase BB isoenzyme in sera of patients undergoing aortocoronary bypass surgery

Creatine kinase BB isoenzyme (CK-BB) was detected intraoperatively in 22 of 25 patients undergoing aortocoronary bypass surgery, both in the coronary sinus and in the mixed venous blood. In a group of 10 patients in whom selective intracavitary profound hypothermic arrest was used, CK-BB values were lower than in another group of 10 patients, in whom controlled ventricular fibrillation with moderate total body hypothermia was instituted. This latter group also had higher levels of CK-MB. Patients who developed acute myocardial infarction immediately prior to or during the surgical intervention had the highest CK-BB values. This enzyme appeared as early as 15 minutes after the institution of cardiopulmonary bypass and disappeared within 6 hours. It is considered that part of the BB isoenzyme in serum of patients undergoing heart surgery is of myocardial origin.

Investigation of cardiorespiratory abnormalities through computer simulation.

Abstract The basic physiologic functions which were simulated on the digital computer are multiple alveolar ventilation through a branching bronchial structure, the distribution of alveolar ventilation across the lung based on airway resistance and alveolar compliance, O2 and CO2 exchange with and transport in the blood, ventilation control based on arterial blood Pa co 2, Pa o 2 and pHa, and peripheral metabolic exchange of O2, CO2, and acid or base. The simulation output is a set continuous-time variables corresponding to clinical measurements, namely: volume, rate and composition of expired gas, composition of arterial and venous blood, indicator dilution across the heart and lung, and intraplural pressure used to obtain dynamic lung compliance and resistance. The simulation was used to investigate the observability (based on the clinical measurements) of changes in ventilation and perfusion distributions and to evaluate the ability of the lung to control acid-base balance with normal and reduced lung compliance for a range of metabolic CO2 production and acid or base, compatible with those observed in critically ill patients in decompensated septic shock.

Structural-functional correlates of reversible myocardial anoxia

Abstract Using the mammary artery-pedicle preparation, the structural-functional response of the canine myocardium to increasing periods of reversible normothermic anoxia was precisely defined. At 15 min there was complete return of structure and function. Sixty minutes of anoxia produced irreversible damage; 30 min resulted in changes that were largely reversible.

Comparison of myocardial preservation techniques for aortocoronary bypass surgery

Abstract The myocardial properties of three different techniques for cardiac arrest during aortocoronary bypass surgery were analyzed. Ventricular fibrillation and moderate total body hypothermia (30–33°C) (Group I) was found to be an insecure method of preservation. It produced a high incidence of focal irreversible ultrastructural changes (7 of 10 patients), high post-bypass CK-MB levels (mean 85.54 U/liter) indicative of myocardial damage, and impaired clinical and physiologic recovery courses. Six out of ten patients needed inotropic support, three had prolonged stay in ICU, and three patients showed Type III (unacceptable) recovery trajectories, one of whom died of myocardial decompensation four weeks after surgery. This method, which was the most common one used in our institution, was completely abandoned as a result of these studies. Potassium induced cardioplegia combined with methylprednisolone sodium succinate, hypertonic glucose and intermittent moderate topical cooling (25–27°C) of the heart (Group III) offered a generally acceptable form of myocardial protection, as only one patient showed irreversible ultrastructural changes. The mean post-bypass CK-MB level was only moderately elevated (mean 22.32 U/liter), but seven of ten patients needed inotropic support. There were no Type III recovery trajectories and two patients showed an optimal Type I recovery. Only one patient had a prolonged stay in ICU, and another patient exhibited electrocardiographic evidence of a perioperative myocardial injury pattern. Selective intracavitary profound hypothermic arrest (15–18°C) (SIPHA) offered the best myocardial protection as evidenced by remarkably well preserved ultrastructure and significantly (P These data also suggest that the major determinant of a successful myocardial preservation is the level of myocardial layer temperature, being best at the lowest temperature (15–18°C), worst at the highest temperature (30–33°C) and intermediate at 25–27°C. Additional injury may also be induced by ventricular fibrillation which by itself increases myocardial metabolic demands.

A Permanent Experimental Model for Reversible Myocardial Anoxia

Abstract A new permanent preparation for studying myocardial response to reversible ischemia was defined and characterized in 46 dogs. The left mammary artery was anastomosed to the second diagonal branch of the left anterior descending coronary artery. The artery distal to the anastomosis served as the sole vascular supply for a myocardial pedicle created by a simultaneous incision and suture technique. The venous drainage was left intact, draining blood to the great cardiac vein and coronary sinus. The pedicles so constructed were an anatomically defined myocardial segment with an independent yet controllable vascular supply that maintained viable, functioning tissue. Functional continuity with surrounding myocardium was preserved. There was no damage to adjacent tissue. Overall ventricular function was maintained, and permanent preparations were readily available for study. Occlusion of the mammary artery for a 15-minute period produced structural and functional changes that were completely reversible with 30 minutes of revascularization. Sixty minutes of occlusion produced severe morphological and functional damage that was only slightly reversible. Additional applications of the model are discussed.

The use of steroids as a potentiator of hypothermic myocardial preservation in man.

Profound hypothermic preservation (15–18°C) of the arrested myocardium offers the best protection against ischemic changes and potassium cardioplegia potentiates this preservation by allowing a more dynamic postbypass recovery, but at the cost of increased intra- and extracellular edema and mitochondrial injury. This study assesses the protective value of a steroid in the perfusion solution, methylprednisolone sodium succinate (1 g/liter), in the presence of profound hypothermic (myocardial T < 20°C) potassium (K = 26 meq/liter) cardioplegia. In a randomized prospective blinded study two groups (control A and steroid B) of 10 patients undergoing a minimum of three coronary bypass grafts were compared by clinical, cardiodynamic, electron microscopic biopsy, and mixed venous lactate and creatine phosphokinase (CK-MB) isoenzyme studies. The mean anoxic arrest time and number of grafts per patient were comparable. Although the CK-MB isoenzyme levels were lower in the postoperative period in the Solu-Medrol group, this was not statistically significant. The clinical course of the two groups was similar, however the control group of patients required a far greater degree and duration of inotropic support to attain comparable recovery trajectories to the Solumedrol group of patients. Critical ultrastructural differences in the steroid-treated group were better mitochondrial preservation, increased perimitochondrial glycogen stores, and a reduction in intracellular edema. These results suggest that steroids may enhance stabilization of cellular metabolic processes under conditions of hypothermic potassium cardioplegia.

Early and Long-Term Effects of Direct Myocardial Revascularization on Cardiac Function: A Prospective Study Using Multivariable Physiological Analysis

Perioperative and late follow-up hemodynamic cardiovascular studies to assess the effects of direct myocardial revascularization on cardiac function objectively have been completed on 51 patients. Analysis of the data delineated three distinct groups basedon the patterns of their early postoperative recovery. Group I patients (12) had a hyperdynamic cardiovascular response to operation and returned to a normal physiological range of cardiac function within 24 hours. Group II patients (24) initially had moderate to severe myocardial decompensation postoperatively but responded to inotropic support and moved into the normal physiological range within 24 to 48 hours. Group III patients (15) had severe, prolonged myocardial decompensation with little response to inotropic support. There were no early deaths in Group I, 1 early iatrogenic death in Group II, and 2 deaths from sepsis, 1 in Group I and 1 in Group II. All 7 cardiogenic deaths occurred in Group III patients. Late follow-up studies 4 to 23 months postoperatively have been completed on 29 patients. These showed cardiovascular stability in the mean values in Groups I and II. Significant improvement in mean cardiac function was seen in surviving Group III patients.

Cardiorespiratory simulation for the evaluation of recovery following coronary artery bypass surgery

Abstract The interpretation of a patients status and recovery after coronary artery bypass surgery are difficult because of the complex interaction of many factors and because only relatively limited, non-specific measurements can be made. The objective of this study was to develop a simulation model of basic cardiorespiratory functions which would be useful as a clinical tool to obtain a refined characterization of a patients cardiopulmonary interactions based on clinical measurements. The simulation was used to generate the same types of measurements obtained on patients. The basic approach was to adjust the simulation parameters so that the simulated measurements agreed with the patients data. Thirty-five patients who had multiple coronary bypass surgery were simulated. The measurements agreed within clinical significance for a wide range of physiologic states. The resulting values of the simulation parameters provide functional indices of ventilation/perfusion disparity, diffusion gradients, venous-arterial pulmonary shunt, and respiratory dead space. The simulation model also offered a technique for estimating the efficacy of cardiorespiratory support maneuvers in changing blood gas and pH values in the critically ill post-coronary-bypass patient with an acute respiratory distress syndrome.

Selective Intracavitary and Coronary Profound Hypothermic Cardioplegia for Myocardial Preservation: A New Technique

A technique is described for selective intracavitary and coronary hypothermic perfusion during cardiac bypass with cardioplegia to facilitate cardiac operations. A cold perfusate (Plasmalyte 148 and mannitol, 12.5 gm/L at 8 degrees to 10 degrees C) is administered with the aid of a low-flow perfusion pump into the left ventricular cavity and coronary circulation through an apical perfusion-venting (Per-Vent) catheter. This perfusate cools the myocardium rapidly and homogeneously to a temperature of 15 degrees to 20 degrees C. Within this temperature range, complete cardioplegia occurs and the safe ischemia period can be extended to 120 minutes. This method was applied in 50 unselected consecutive adult patients undergoing aortocoronary saphenous vein bypass grafting or aortic or mitral valve replacement. All patients survived and had excellent recovery of ventricular function.

Estimation of blood gas contents from expired air under normal and pathologic conditions

Methods of estimating arterial-venous O2 content difference, mixed venous CO2 content and tension, and average arterial CO2 content are presented. They are based on the continuous gas analysis of expired air during a prolonged expiration. The influence of CO2 storage in lung tissue and certain pathophysiologic conditions on the accuracy of these methods was systematically investigated with a comprehensive multi-chamber computer simulation of the lung. For normal levels of CO2 storage capacity, satisfactory estimates of arterial-venous O2 content difference are feasible for differences less than 8 volumes percent; with high levels of CO2 storage capacity, large errors can occur. Storage of CO2 in lung tissue causes large errors in the estimates of mixed venous CO2 content and tension, and average arterial CO2 content; reliable estimates do not appear to be feasible from analysis of expired gas. Simulated pathophysiologic conditions of interstitial pulmonary edema or atelectasis also introduce large errors. This analysis delineates the theoretic limitations of an estimation technique in clinical applications where acute respiratory dysfunctions occur.