Importance of acid-base strategy in reducing myocardial and whole body oxygen consumption during perfusion hypothermia.

During induced hypothermia with cardiopulmonary bypass, acid-base management usually follows one of two strategies: the so-called ectothermic or alpha-stat strategy, in which the pH of the arterial blood increases 0.015 pH units for every degree Celsius decrease in body temperature, or the pH-stat strategy, in which pH remains 7.4 at all temperatures. It has been assumed that oxygen consumption decreases approximately equally during hypothermia with either strategy, although there are biochemical reasons to hypothesize that oxygen consumption would be better maintained with the alpha-stat strategy. We also hypothesized that venous oxygen tension would be lower with the more alkaline alpha-stat strategy than with the pH-stat acid-base strategy, because of the Bohr effect. We tested these hypotheses by placing 10 anesthetized immature domestic pigs on cardiopulmonary bypass. We measured whole body oxygen consumption and myocardial oxygen consumption. Control measurements were made at 37 degrees C. Then the animals were cooled to 27 degrees C and the measurements were repeated. The alpha-stat strategy (pH 7.554 +/- 0.020 at 27 degrees C) was used in five animals and five animals received pH-stat management (pH 7.409 +/- 0.012 at 27 degrees C). Whole body and myocardial oxygen consumption rate decreased in both groups, but more so in the alpha-stat animals than in the pH-stat animals. The unexpectedly high oxygen consumption in the pH-stat animals also resulted in a lower than expected venous oxygen tension. Thus the effect of hypothermia in reducing oxygen consumption was less pronounced with pH-stat acid-base management.

Comparison of myocardial temperatures with multidose cardioplegia versus single-dose cardioplegia and myocardial surface cooling during coronary artery bypass grafting.

Myocardial hypothermia with multidose cardioplegia has not been compared with single-dose cardioplegia and myocardial surface cooling with a cooling jacket in patients having coronary artery bypass grafting. In this study, 20 patients with three-vessel disease undergoing coronary bypass at 28 degrees C with bicaval cannulation, caval tapes, and pulmonary artery venting (4.9 +/- 0.7 grafts per patient) were prospectively randomized equally into group I (multidose cardioplegia) and group II (single-dose cardioplegia with a cooling jacket). The initial dose of cardioplegic solution was 1000 ml. Group I then received 500 ml of cardioplegic solution every 20 minutes, delivered into the aortic root and available grafts. In group II, after the cardioplegic solution had been administered, a cooling jacket covering the right and left ventricles was applied. In both groups temperatures were recorded every 30 seconds at five ventricular sites: (1) right ventricular epicardium; (2) right ventricular myocardium or cavity, 7 mm; (3) left ventricular epicardium; (4) left ventricular myocardium or cavity, 15 mm; and (5) septum, 20 mm. Group mean temperatures at each site at various times were compared within each group and between the two groups by analysis of variance. Aortic crossclamp time was 60.3 +/- 12.1 minutes in group I and 52.8 +/- 7.3 minutes in group II (p = 0.12); cardiopulmonary bypass time was 103.7 +/- 11.1 minutes in group I versus 87.7 +/- 12.7 minutes in group II (p less than 0.01). One minute after the cardioplegic solution was initially given, temperatures between groups at each site were not statistically different, but left ventricular epicardial temperatures within both groups were significantly higher than in the other four sites. Nineteen minutes after administration of the cardioplegic solution, temperatures in group I at all sites were higher than in group II. Similarly, throughout the entire period of aortic crossclamping, mean temperatures (except left ventricular myocardial site), maximum temperatures, and percentage of time all temperatures were 15 degrees C or higher were greater in group I than in group II. The following conclusions can be reached: 1. Initial myocardial cooling with 1000 ml of cardioplegic solution is not significantly limited by coronary artery disease but is suboptimal (16 degrees or 17 degrees C) in the inferior left ventricular epicardium because of continual warming from the aorta and subdiaphragmatic viscera. 2. Without myocardial surface cooling, excessive external myocardial rewarming to 18 degrees to 22 degrees C occurs within 20 minutes at all sites after delivery of the cardioplegic solution.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical comparisons of methods of myocardial protection.

Currently, numerous methods are in use for myocardial hypothermia as a myocardial preservation modality for cardiac operations. During cardiac ischemia we have compared myocardial surface cooling with topical cold saline (Group I, N = 9), crystalloid cardioplegia plus topical cold saline (Group II, N = 8) and cardioplegia with a specially designed cooling jacket (Group III, N = 8) in patients undergoing aortic or mitral valve replacement, or both. Temperatures were assessed and recorded continuously in standardized locations for the right and left ventricular epicardium and endocardium. In Group I the rate of cooling was significantly slower than in the other two groups. Also, excessive gradients were developed across the left and right ventricular walls. In Group II the rate and depth of cooling were adequate and initial temperature gradients were eliminated. However, over the period of ischemia, significant rewarming occurred. In Group III temperatures were reduced rapidly and uniformly and maintained at or below 10 degrees C for the duration of the ischemic period. These differences are statistically significant (p less than 0.05). For optimal myocardial hypothermia, we recommend the following: separate cannulation of the superior and inferior venae cavae with caval snares; venting of the pulmonary artery (if inadequate, pulmonary vein occlusion or direct left atrial venting); induction of myocardial hypothermia with crystalloid or cold blood cardioplegia; and maintenance of hypothermia by the cooling jacket described herein. It is also desirable to continuously monitor temperatures of the right and left ventricular endocardial and epicardial surfaces.

Decreased critical mixed venous oxygen tension and critical oxygen transport during induced hypothermia in pigs.

The effects of hypothermia on oxygen delivery and tolerance to hypoxia were studied in 8 normothermic (36.8 degrees C) and 10 hypothermic (29.3 degrees C) pigs that had been anesthetized and surgically implanted with instruments. Cardiac output (QT), VO2 [oxygen consumption, or QT X C(a-v)O2, where C(a-v)O2 is arteriovenous oxygen content difference], arterial and mixed venous blood gas values, and lactate concentrations were measured as the animals were made progressively hypoxic. Under control, normoxic conditions, mixed venous oxygen tension (PvO2) was 41.4 +/- 2.1 mm Hg (mean +/- SE) in the normothermic animals and 26.1 +/- 1.6 mm Hg in the hypothermic animals; these values are close to those predicted in our previous theoretical analysis. To study tolerance to hypoxia during hypothermia, critical PvO2 and critical total oxygen transport (TOT = QT X CaO2, where CaO2 is oxygen content of arterial blood) were determined by decreasing the inspired oxygen concentration (FIO2) in steps and measuring the point where VO2 and blood lactate levels became PO2 or TOT dependent. Again as predicted, the critical PVO2 was lower in the hypothermic animals (15.5 +/- 1.0 mm Hg at 29.3 degrees C compared with 22.0 +/- 1.4 mm Hg at 36.8 degrees C), but critical venous oxyhemoglobin saturation values were not statistically different at the two temperatures. Critical TOT was also decreased during hypothermia, as was the margin of reserve in both PVO2 and TOT (the difference between the normoxic and the critical values).

Temporary extracorporeal support of the right ventricle.

Six patients having severe right ventricular failure after cardiac surgical procedures were treated temporarily with an extracorporeal pump to bypass the right ventricle. The initial operative procedures included coronary artery bypass procedures with and without concomitant valvular and aortic replacement. A Biomedicus centrifugal pump was used as the right ventricular assist device in most cases. The assist period ranged from 3 to 96 hours, and an intra-aortic balloon pump was used in five of the six patients. All patients initially responded to the right ventricular assist device, four were successfully weaned, and one patient is a long-term survivor. The use of a right ventricular assist device is not difficult or complicated and can be lifesaving for those patients having potentially reversible profound right ventricular failure.

Theoretical analysis of oxygen transport during hypothermia.

Oxygen transport and delivery to peripheral tissues during hypothermia are analyzed theoretically, taking into consideration various conditions observed both in nature and clinically. With decreasing temperature, P50 (the oxygen tension [PO2] at 50% hemoglobin saturation with oxygen) decreases, thereby leading to low mixed venous oxygen tension (PvO2) and thus low tissue PO2 values. On cooling from 37 degrees C to 25 degrees C at pH 7.4, the P50 decreases from a normal 26.8 mm Hg to 13.2 mm Hg. In the intact animal, as well as in a patient on cardiopulmonary bypass, oxygen consumption (Vo2) and cardiac output (QT, or recommended pump flow rate) decrease. If the ratio of Vo2/QT remains constant, then the arteriovenous O2 content difference, C(a-v)O2, must remain constant. If C(a-v)O2 is 5 ml/dl, we calculate that the PvO2 must decrease from a normal 40 mm Hg to 26.8 mm Hg at 25 degrees C. Clinically induced hypothermia is usually accompanied by hemodilution of the patient's blood to 50% normal hematocrit, which would reduce PvO2 to 13.7 mm Hg. Use of constant relative alkalinity (pH = 7.58 at 25 degrees C) further reduces the P50 to 10.8 mm Hg and the PvO2 to 10.9 mm Hg. Other clinical situations are also discussed. Sensitivity analysis predicts that during hypothermia PvO2 (and thus tissue PO2) is very dependent on P50, hemoglobin concentration, and QT, and less dependent on oxygen solubility and arterial PO2. We conclude that monitoring of mixed venous or tissue PO2 might be advisable, and that blood flow is the component of oxygen transport most amenable to manipulation by the clinician to ensure adequate tissue oxygenation during induced hypothermia.

Quantitative evaluation of the myocardial preservative characteristics of nifedipine during hypothermic myocardial ischemia.

Nifedipine, a slow calcium-channel blocker, has been used to preserve myocardial function in the ischemic heart. To quantitatively evaluate the effectiveness of nifedipine as a cardioplegic agent during moderate hypothermia (28 degrees C), 15 pigs were evaluated on total and right heart bypass with measurement at normothermia and after 1 hour of hypothermic ischemia of stroke volume, coronary blood flow, myocardial oxygen consumption, and lactate extraction. Myocardial tissue gases (oxygen and carbon dioxide) were continuously monitored. Animals were divided into three groups: hypothermic ischemia, hypothermic ischemia with infusion of nifedipine carrier without nifedipine, and hypothermic ischemia with nifedipine and its carrier. A significant decrease in stroke volume was seen in all three groups; however, the depression was significantly greater following hypothermic ischemia than following cardioplegia with either nifedipine or its carrier. The mean recovery value of stroke volume was highest in the nifedipine group, but this difference between nifedipine and its carrier alone did not reach statistical significance. Coronary blood flow, myocardial oxygen consumption, lactate extraction, and tissue gases failed to substantiate a significant benefit when nifedipine was compared with its carrier alone. We conclude that under these hypothermic conditions, no proven statistically significant advantage was noted in the nifedipine group when compared with the nifedipine carrier group in swine. However, both nifedipine and the carrier were superior as a myocardial preservative when compared with hypothermic ischemic arrest alone.

Naloxone: ineffective in improving cardiac performance after hypoperfusion in swine.

A study was done to measure beta-endorphin immunoreactivity (beta-EI) in swine subjected to cardiopulmonary bypass at normal aortic perfusion pressures and during low-flow states such as can occur with shock. Fifteen pigs, divided into three groups of five each, were placed on total and right heart bypass and perfused as follows: group I, normal blood pressure (80 mmHg); group II, low blood pressure (45 mmHg); and group III, low flows (25 ml/kg/hr). beta-endorphin immunoreactivity was assayed six times during the procedure. Ventricular performance was evaluated by measuring stroke volume (SV) while controlling preload, afterload, and heart rate. Determinations of SV were made at the beginning of bypass, after a 1-hr pump run, and after administration of naloxone (1.1 mg/kg). There were no significant changes in beta-EI in any of the groups during the study. The initial SV in group III (23 +/- 6 ml) decreased significantly (p less than 0.05) after 1 hr of decreased cardiac perfusion (8.0 +/- 7 ml) and was not improved by naloxone (5.0 +/- 7 ml). Ventricular performance was not improved in any group following naloxone administration. In our study, naloxone administered to swine following inadequate myocardial perfusion did not effect a significant cardiac hemodynamic response.

Sonomicrometry: its application as a routine monitoring technique in cardiac surgery.

We utilized ultrasonic-dimension crystals in approximately 50 patients during a three-year period to evaluate clinical sonomicrometry as a routine monitoring tool in patients undergoing cardiac operations. Standard research piezoelectric pulse transit ultrasonic transducers were modified with a hooked attachment in a tethered configuration to facilitate accurate alignment and quick insertion for the measurement of myocardial segment length changes. These segment crystals were used both intraoperatively and postoperatively to evaluate the left ventricular pressure-geometry relationships and to serve as a continuous monitor of myocardial function. The left ventricular pressure-volume relationship was varied by temporarily reapproximating the pericardium (pericardial closure resulted in a 12% reduction in fractional shortening, a 5% decrease in end-diastolic segment length, and an 8% increase in pulmonary artery diastolic pressure). During both the intraoperative and postoperative periods, we found good correlation between thermodilution, stroke volume, and myocardial dimensions; no correlation was noted between pulmonary artery diastolic pressure and stroke volume. No bleeding or major complications resulted from the use of these sonomicrometry transducers. Our initial clinical experience with sonomicrometry seems to support its use as a potentially valuable monitoring tool.

Evacuation of calcific valvular debris using a standard Ellik evacuator.

A simple but effective technique is described for removing calcific and other debris following aortic and mitral valve replacement. This technique uses an Ellik evacuator , which is readily available in most operating rooms. An 11-year experience is presented, documenting the efficacy of this method in several hospitals.

The physiologic effects of oxygen transport by hemoglobin solutions.

Two chronic animal models and one acute animal model were used to evaluate exchange transfusion with stroma-free hemoglobin solutions. A direct comparison was made between stroma-free hemoglobin solutions having differing oxygen offloading characteristics as well as a colloid solution consisting of 7% bovine albumin. These studies involved a partial exchange involving approximately 50% of the animal's blood volume to simulate a clinically more appropriate partial blood replacement situation. We noted a consistent increase in the arterial oxygen content of animals exchanged with the stroma-free hemoglobin solutions and some modest improvement in oxygen dynamics. Our studies examining myocardial contractility, especially those carried out in the right heart bypass swine preparation failed to substantiate any difference between an exchange with albumin or stroma-free hemoglobin solutions. The conscious animal models examined both at rest and at exercise demonstrated marked differences in exercise response. Animals exchanged transfused with stroma-free hemoglobin solutions often had an almost normal exercise response while those animals exchanged with non-oxygen carrying albumin solution frequently failed to exercise on a treadmill. Blood flow measurements using radiolabeled microspheres were performed in chronically instrumented swine. These animals had a normal variation in organ blood flow during exercise which was noted both during the control period as well as following exchange with stroma-free hemoglobin solutions. Animals exchanged transfused with albumin had a marked derangement in organ blood flow apparently reflecting the decreased oxygen availability. Results from these three studies substantiate a significant benefit to animals undergoing a 50% exchange when that exchange is done with an oxygen carrying solution such as stroma-free hemoglobin solutions as opposed to a non-oxygen carrying but oncotically active solution such as albumin solution. These studies seem to offer encouragement to the continued investigation and ultimate clinical utilization of hemoglobin solutions as an appropriate blood substitute.

Effectiveness of stroma-free hemoglobin solution as seen in a right heart bypass swine model.

To determine if tolerance to severe anemia (Hct less than or equal to 10%) might be improved with stroma-free hemoglobin solution (SFH), 15 swine were placed on normothermic right heart bypass (RHBP) for evaluation of stroke volume (SV), coronary blood flow (CBF), arterial-coronary sinus oxygen content difference S(a-cs)O2, and myocardial oxygen consumption (MVO2) during a control period at a hematocrit (Hct) level of 30%. These 15 animals, divided into three equal groups, subsequently underwent exchange transfusion either to a Hct of 5% using 7% SFH (group 1), or to a Hct of 5% (group 2) or 10% (group 3) using 7% bovine albumin solution. All tests were repeated during these experimental conditions. Myocardial performance after albumin solution exchange was sustained on RHBP in only 1 of 10 animals. SFH animals (group 1) had a significant drop in SV at 14 torr after exchange (20 +/- 3 ml vs 10 +/- 4 ml, p less than 0.025), but this 50% performance level could be sustained. CBF rose and MVO2 fell in all groups, although the statistically nonsignificant mean differences were less with SFH. S(a-c)O2 fell significantly (p less than 0.05) with albumin solution (group 2 7.3 +/- 1.4 vs 2.2 +/- 0.2, group 3 8.9 +/- 2.0 vs 3.8 +/- 1.0), and nonsignificantly with SFH (5.6 +/- 0.7 vs 4.1 +/- 1.4). Although myocardial performance decreased with SFH, the authors believe these comparative results support the use of SFH at an Hct of 5%.

Theoretical analysis of optimal P50.

A simple expression is derived to describe the partial pressure at 50% hemoglobin saturation with oxygen (P50) that maximizes venous oxygen tension (PO2) for a given arterial PO2 and oxygen consumption. That "optimal P50" also maximizes arteriovenous saturation differences for given arterial and venous PO2 values. The optimal P50 can be expressed as the square root of the product of arterial and venous PO2 values. Alternatively, it can be expressed as a simple function of the arterial PO2 and the arteriovenous saturation difference. Nomograms summarize the relationships between the variables, and published observations that suggest an observational basis for our theoretical analysis are reviewed. We conclude that for normoxia or moderate hypoxia a high P50 is advantageous, whereas for more severe hypoxia or increased metabolic demands, a low P50 is advantageous.

Effect of albumin and mannitol on organ blood flow, oxygen delivery, water content, and renal function during hypothermic hemodilution cardiopulmonary bypass.

The present study was designed to determine if the addition of albumin or mannitol to the priming solution of the pump oxygenator would diminish edema in organs, without diminishing some of the beneficial effects of hemodilution on blood flow and renal function. Tissue blood flow (15 mu spheres), water content, and renal clearances were determined in 8 animals during cardiopulmonary bypass. A 2(2) factorial, completely fixed experimental design was used. All animals were placed on cardiopulmonary bypass with hemodilution (hematocrit 25 +/- 2%) and hypothermia (25 degrees +/- 1 degree C). Albumin decreased flow to the midmyocardium of the left ventricle and to the spleen, and increased flow to the inner cortex of the kidney. Albumin caused decreased urine flow and decreased urine sodium, and also diminished renal osmolar, sodium, and free-water clearances. both mannitol and albumin decreased lung water. Mannitol decreased water content of the outer renal cortex, and decreased flow to the inner cortex and medulla of the kidney and to the spleen. Mannitol had no significant effect on urine flow, renal plasma flow, or renal clearances. Neither albumin nor mannitol had any effect on water content of the intestine, stomach, liver, or myocardium where the greatest accumulation of water occurs with hemodilution. The effect of albumin on renal function is potentially deleterious during cardiopulmonary bypass because it decreases urine flow, and osmolar and free-water clearance.

Blood conservation techniques.

Increasing numbers of operations requiring cardiopulmonary bypass have been accompanied by greater demands for blood resources. Improved techniques of blood conservation have diminished the average blood requirements per operation and have increased the percent of operations that can be done without homologous blood. The conservation of blood can be planned according to each patient's requirements. The techniques include preoperative blood donation, intraoperative withdrawal of blood, reinfusion of oxygenator blood, autotransfusion of blood after heparin neutralization, autotransfusion after wound closure, and hemodilution. The availability of techniques for filtration, centrifugation, and washing of blood have improved the safety of autotransfusion. The techniques that gives the best cost/benefit ratio appear to be preoperative withdrawal of blood, reinfusion of centrifuged oxygenator contents, and reinfusion of filtered blood from chest drainage.

Effects of halothane and morphine sulfate on myocardial compliance following total cardiopulmonary bypass.

We evaluated the effect on diastolic myocardial compliance of halothane and morphine sulfate using 15 swine placed on total cardiopulmonary and right heart bypass with controlled aortic pressure, heart rate, and left ventricular preload. The animals were divided into three equal groups: (I) regional block anesthesia, (II) morphine sulfate (10 mg/kg), and (III) halothane anesthesia at 0.5%. Myocardial performance was evaluated on right heart bypass following a 30 minute period of total cardiopulmonary bypass before and after administration of the anesthetic agent by measuring stroke volume, left ventricular end-diastolic pressure, and left ventricular end-diastolic volume. All perfusions were at normothermia, at a hematocrit level of 30%, and at a normal arterial Po2. PCO2, and pH. Neither regional block nor morphine sulfate anesthesia significantly depressed the myocardium or changed diastolic compliance. Halothane, however, significantly decreased diastolic compliance so that stroke volume was less at a given left ventricular end-diastolic pressure, but not at a given left ventricular end-diastolic volume. The depression of stroke volume with halothane following cardiopulmonary bypass at equal filling pressures appears to be due primarily to a change in compliance rather than to a change in contractility.