John H. Rousou

Myocardial High-Energy Phosphate Replenishment during Ischemic Arrest: Aerobic versus Anaerobic Metabolism

An in vivo, isolated pig heart preparation was used to study the effect of L-glutamate added to crystalloid and blood potassium cardioplegia on the myocardial high-energy phosphate compounds, adenosine triphosphate (ATP) and creatine phosphate (CP). Studies were performed during a three-hour arrest interval and during 60 minutes of reperfusion. Levels of ATP remained at or above control levels during arrest in animals receiving either unmodified blood or glutamate-enriched crystalloid cardioplegia. While glutamate significantly improved the ability of the crystalloid solution to preserve ATP during arrest, when added to blood, it contributed to a depressed ATP after a three-hour arrest. Creatine phosphate declined during arrest in all animals, but those receiving unenriched blood cardioplegia consistently had the highest levels (p less than 0.05). Addition of glutamate to crystalloid cardioplegia provided a significantly (p less than 0.05) higher level of CP at the end of three hours of arrest, which was still lower than that noted with unenriched blood. Comparable to its effect on the ATP level, when glutamate was added to blood cardioplegia, a decrease (p less than 0.05) in CP was noted after three hours of arrest. Attempts to enhance high-energy phosphate production by supplementing blood cardioplegia with L-glutamate are ineffective, while increased high-energy phosphate production results when glutamate is added to crystalloid cardioplegia. This implies that L-glutamate functions where anaerobic and not aerobic metabolism is the major component of preservation. With reperfusion, the only group of animals displaying depressed levels of ATP and CP was that receiving glutamate-enriched blood cardioplegia.

Fluosol-Da: An Artificial Blood for Total Cardiopulmonary Bypass

The isolated, in situ pig heart model was used to determine if Fluosol could support myocardial function during cardiopulmonary bypass. Fourteen pigs were utilized; 7 underwent studies of myocardial metabolism (coronary blood flow and vascular resistance, myocardial oxygen consumption and extraction, lactate extraction, and adenosine triphosphate and creatine phosphate levels), and 7 underwent studies of myocardial contractility and compliance (intraventricular balloon measurements). Each study was carried out utilizing one hour of control hemic perfusion, followed by one hour of Fluosol perfusion, and followed by a third hour of a return of hemic perfusion. The results documented that in the vented, beating, nonischemic heart, myocardial metabolism and functional measurements are maintained during an hour of Fluosol perfusion. However, because of an increased level of ionized calcium during Fluosol perfusion, myocardial functional measurements document significantly increased contractility. The increased contractility is associated with an increase in anaerobic metabolism. The latter contributes to a decline in the high-energy phosphate level following a return of hemic perfusion as the heart recovers from the increased work load placed on it during Fluosol perfusion. It is concluded that here is sufficient oxygen-carrying capacity in Fluosol-DA to maintain cardiac function during perfusion in the large animal model. However, the carrier solution for the Fluosol must be adjusted to appropriate electrolyte content to avoid adverse effects on the myocardium.

Modified Fogarty clamp for the fragile aorta.

Abstract The Fogarty aortic hydragrip clamp is adequate to clamp the normal aorta during open-heart operation. The fragile aorta, however, requires a more delicate occlusion than that provided by the slim, rather rigid clamping jaws of the Fogarty clamp. To prevent the crushing effect of a Fogarty clamp on a fragile aorta, a simple modification has been devised and is described here.

The Optimal Potassium Concentration in Cardioplegic Solutions

High-energy phosphates provide a sensitive index of myocardial preservation. This experiment was designed to use this index in order to assess the efficacy of various potassium concentrations in a crystalloid cardioplegic solution in protecting the myocardium during hypothermic ischemic arrest. The in vivo ischemic pig-heart model was used, measuring left ventricular levels of adenosine triphosphate (ATP) before, during, and after a two-hour arrest period and after 30 minutes of reperfusion. Thirty-eight animals were divided into seven groups of 5 to 6 animals each. Each group received a different potassium concentration in the cardioplegic solution, namely, 5, 10, 15, 20, 25, 30, and 35 mEq/L. The results were as follows: the ATP moiety was best preserved during ischemia and reperfusion in the 15 mEq/L group, while it remained significantly lower in the 5 mEq/L group. The 10, 20, 25, 30, and 35 mEq/L groups showed an intermediate range of ATP preservation. We conclude from these results that cardioplegic solutions containing 5 mEq/L of potassium seem to be inadequate for myocardial preservation during ischemic arrest; that solutions with 15 mEq/L of potassium may offer the best myocardial protection of all concentrations tested; and that solutions with potassium concentrations of 15 and 35 mEq/L are significantly better than normokalemic (5 mEq/L) cardioplegic solutions.

Experimental evaluation of secondary blood cardioplegia

Reperfusion damage after ischemia may be evidenced by myocardial cell edema, intracellular calcium accumulation, and limited utilization of oxygen. The need for cardioplegic arrest during initial reperfusion to allow oxygen to be used for reversing ischemic damage rather than for electromechanical activity has been propounded by some researchers. Reports of greater postischemic compliance and performance, low postischemic edema, and greater oxygen uptake at a perfusion pressure of 50 mm Hg or lower have been cited. The present study was conducted on 24 pigs having 2-hr cardioplegic arrest, which of 12 underwent normal reperfusion and 12 experienced secondary cardioplegia followed by normal reperfusion. The results showed that in spite of improved high-energy phosphate preservation, the secondary cardioplegia group had higher myocardial edema, less coronary flow, and poorer contractility and compliance at the end of 1 hr of reperfusion. Because of these findings and contradictory results reported by other groups, caution is urged in the clinical extrapolation of the results of such studies pending further investigations.

Residual metabolism of the hypothermic-arrested pig heart

Abstract Fourteen Yorkshire pigs were anesthetized and placed on cardiopulmonary bypass. The hearts were cooled to 15°C and arrested with periodic injections of 50 ml of a cold ( T = 4°C) crystalloid cardioplegic solution containing 35 meq/liter K + for 2 hr. The hearts were then reperfused with warm oxygenated blood for 1 hr. A needle pH electrode (MI-408C, Microelectrodes, Inc., Londonderry, N. H.) was placed into the myocardium and measurements of tissue pH were taken during arrest and reperfusion. Tissue samples were taken during arrest and reperfusion and analyzed for their content of ATP, ADP, AMP, CP, and lactic acid. Blood samples were taken during reperfusion for measurement of CPK. Tissue concentrations of ATP and CP fell during arrest from 4.10 and 6.54 to 3.40 and 1.45 m M respectively. The concentrations of H + and of lactic acid rose during arrest from 2.8 × 10 −8 M and 10.48 m M to 27.5 × 10 −8 M and 18.95 m M , respectively. During reperfusion ATP continued to fall to 2.95 m M while blood CPK rose from 50.81 to 159.49 IU/L. The rise of H + during hypothermic arrest indicates the presence of residual metabolism which may have irreversibly changed the enzyme system for regulating the concentration of tissue ATP. Evidence for this conclusion is given by the escape of CPK into blood during reperfusion.

Performance of pig heart after 30 or 120 minutes hypothermic arrest

The effect of the duration of hypothermic (T = 15°C) potassium cardioplegic arrest and ischemia on the heart was determined by measuring the response of the isolated in situ pig heart to 180 min of perfusion (n = 12) to provide appropriate control values for the study of 30 (n = 25) or 120 (n = 27) min of ischemia, followed by 60 min of reperfusion. In some of these animals, myocardial tissue samples were obtained for measurement of adenosine triphosphate (ATP) and creatine phosphate (CP), (6 in the perfusion group, 7 in the 30 min of ischemia and 60 min of reperfusion group and 15 in the 120 min of ischemia and 60 min of reperfusion group). In the remaining animals, measurements of either left ventricular performance (LVP), myocardial oxygen metabolism (MVO2) or plasma creatine kinase (CK) were obtained (6 in the prolonged perfusion group, 12 in the 120 min of ischemia and 60 min of reperfusion group, [6 LVP and MVO2 and 6 CK] and 18 in the 30 min of ischemia and 60 min of reperfusion group [13 LVP, 17 MVO2 and 6 CK]). During prolonged perfusion, left ventricular performance, expressed as developed pressure, ΔP, fell from an initial value of 175 ± 36 to 128 ± 19 mm Hg at 30 min of perfusion, followed by a more gradual decline to a final value of 113 ± 8 mm Hg at 180 min of perfusion. These decreases were not significantly lower than the initial value. The percentage of myocardial extraction declined in a similar manner, but coronary blood flow was constant over this interval. The primary effect of 30 or 120 min of ischemia was to reduce left ventricular developed pressure, ΔP, during reperfusion to more than 70% of the corresponding value in the control group (these differences were statistically significant) which suggests that prolonging the period of ischemia did not cause further deterioration of cardiac performance. The plasma concentration of CK rose in the control group of hearts subjected to prolonged perfusion from an initial value of 35 ± 6 to a final value of 59 ± 8 IU/liter (P < 0.05). While plasma CK increased during reperfusion in both ischemia/ reperfusion groups, these values were not significantly higher from prearrest values. Thus hypothermic cardioplegic ischemia of this duration did not appear to result in tissue necrosis, but there was a significant reduction in left ventricular performance which was independent of the duration of ischemia between the limits of 30 and 120 min.

The Effect of Acute Coronary Artery Occlusion during Cardioplegic Arrest and Reperfusion on Myocardial Preservation

A study was undertaken to evaluate the effect of acute occlusion of a coronary artery during cardioplegic arrest on myocardial preservation and to elucidate the influence of reestablishment of flow versus continued occlusion during the phase of myocardial reperfusion. Coronary occlusion was simulated, and myocardial viability was determined by measuring tissue levels of adenosine triphosphate (ATP) and creatine phosphate (CP) in biopsies of the posterior left ventricular wall. Eighteen pigs were divided into three equal groups consisting of animals with (1) patent right coronary arteries during arrest and reperfusion, (2) occluded right coronary arteries during arrest and patent during reperfusion, and (3) occluded right coronary arteries during arrest and reperfusion. The results of ATP and CP measurements showed that while poorer protection was afforded during two-hour arrest when the coronary artery was occluded, the risk of damage was much greater during reperfusion. Failure to restore adequate blood flow by retention of occlusion caused a concurrent decrease in ATP and CP levels below prescribed limits of myocardial tolerance. When occlusion occurs in the clinical setting, impeding cardioplegia and reperfusion, the importance of revascularization is emphasized.

A technique of myocardial preservation perfusion.

We present a technique for administering cold cardioplegia that permits the pump technician to conveniently give the fluid. The method is comparable to that used in providing coronary perfusion for aortic valve procedures because it allows controlled volume flow and perfusion pressure. In addition, the technique is inherently safe from infusion of air bubbles.

Left Ventricular Venting during Cardioplegic Arrest

A technique is described for venting the left ventricle during ischemic arrest without cannulation of the ventricle. This approach is ideally suited for coronary revascularization.