Metabolic and haemodynamic changes in the heart during the early phase of cardiopulmonary bypass: II. Animal experiments.

A significant release of lactate instead of uptake was observed during the first 10 min of cardiopulmonary bypass preceding aorto-coronary bypass surgery in human patients. To clarify these findings in more detail, myocardial lactate and oxygen metabolism was studied in healthy dog hearts subjected to a protocol similar to the clinical situation. In one group (n = 11) normothermia at 34 degrees C was used with an empty beating heart, and in the other group (n = 11) hypothermia with ventricular fibrillation was applied. Within the first 10 min of bypass no significant changes in high energy phosphates were observed in myocardial biopsies. However, a marked decrease in mean aortic blood pressure and a simultaneous lowering in oxygen consumption was observed in both groups after instalment of bypass. An initial shift from lactate uptake to lactate release occurred while on bypass in the normothermia group. After 10 min of bypass, lactate uptake was restored in hearts of both groups. Therefore, the lactate release during the initial phase of bypass in patients originates both from the instalment of the bypass and from (local) inadequate perfusion, which is most likely to be due to stenosed coronary arteries.

Changes in myocardial high-energy phosphate stores and carbohydrate metabolism during intermittent aortic crossclamping in dogs on cardiopulmonary bypass at 34 degrees and 25 degrees C.

The effect of cooling to 25 degrees C on myocardial metabolism was studied during four periods of global ischemia (10 minutes each) followed by 15 minutes of reperfusion in dogs on cardiopulmonary bypass. Systemic and heart temperature at normothermia (group N, 34 degrees C; n = 15) was compared with general hypothermia (group H, 25 degrees C; n = 16). Before and at the end of each aortic crossclamp period in small myocardial biopsy specimens the adenosine triphosphate, creatine phosphate, inorganic phosphate, glycogen, and lactate content was analyzed. Also, lactate and inorganic phosphate were measured in the coronary effluents during the repetitive periods of reperfusion. Hemodynamic function was not different at 60 minutes after cardiopulmonary bypass compared with pre-cardiopulmonary bypass values, and was not different between the groups N and H. The tissue content of adenosine triphosphate and glycogen decreased progressively during the experimental period, resulting in slightly depressed values in both groups at the end of cardiopulmonary bypass. Pronounced effects of ischemia and reperfusion on tissue content of creatine phosphate, inorganic phosphate, and lactate were observed after each period of ischemia. The net decrease in tissue creatine phosphate content was not different between groups N and H (41 +/- 4 versus 38 +/- 4 mumol.gm-1 dry weight; mean +/- standard error of the mean) after 10 minutes of ischemia. However, during ischemia the net inorganic phosphate increase in myocardial tissue was significantly higher in group H (70 +/- 7 mumol.gm-1) than in group N (44 +/- 3 mumol.gm-1). These findings do not support the notion that myocardial protection is improved during hypothermia. Moreover, quantitatively the release of inorganic phosphate and lactate did not correlate with the amount accumulated in the myocardial tissue during the preceding periods of ischemia. The release appeared to be temperature dependent, that is, significantly reduced at 25 degrees C. The present data demonstrate why clinical outcome is satisfactory in both surgical procedures, when in general the periods of aortic crossclamping do not exceed 10 minutes each and the reperfusion periods in between the ischemic episodes last about 15 minutes. Besides, the findings indicate that hypothermia is not strictly necessary under these circumstances.

Propagation velocity and reflection of pressure waves in the canine coronary artery.

In this study the pressure wave velocity in the anterior descending branch of the left coronary artery (LADC) of the dog was measured by determining the delay time between pressure pulses along this artery. This method can only be applied if reflections of the pressure wave distal to the sites of pressure measurement are insignificant. From araldite casts of the coronary arteries the following relation between the diameter proximal to (dprox) and distal to (ddist 1, ddist 2) a bifurcation was found: dprox2.55 = ddist12.55 + ddist 22.55, indicating that reflections at a bifurcation areminimal. In dogs reflections were studied by inducing during diastole a pressure pulse in the aorta and measuring pressure and volume flow proximal to and pressure distal to a segment of the LADC at various levels of the coronary peripheral resistance. Reflection of high-frequency components (greater than 7 Hz) was found to be insignificant, allowing application of the above-mentioned method for measuring the wave-front velocity, which is insensitive to low-frequency reflection. At a pressure in the LADC of 13.3 kPa this velocity was 8.6 +/- 1.4 m.s-1 (mean +/- SD). The calculated dynamic cross-sectional stiffness (deltaP/(deltaA/A)) of the LADC was 97 +/- 11 kPa (mean +/- SE) at an arterial pressure of 13.3 kPa.

Coronary artery stenosis controlled by distal perfusion pressure: description of the servo-system and time-dependent changes in regional myocardial blood flow.

An animal model for the induction of coronary artery stenosis is described. In this model the degree of stenosis, as induced with commercially available hydraulic occluders, can be easily controlled by keeping constant the mean perfusion pressure (pcor) distal to the site of stenosis. This pcor is the input signal for a servo-system feeding a motor-pump, which determines the degree of inflation of the cuff around the left anterior interventricular coronary artery (LAICA). In each experiment pcor did not vary more than 2 mm Hg from the preset value of about 25 mm Hg. In 60 anesthetized open-chest dogs the time course of standard hemodynamic variables and regional myocardial blood flow in the center of the underperfused area, using the radioactive microsphere technique, were determined. Within 1 min after induction of stenosis heart rate and end-diastolic left ventricular pressure (plved) increased (by 20 and 60%, respectively) and mean aortic pressure and dplv/dtmax decreased (by 10 and 25%, respectively). After the initial decrease median myocardial blood flow further decreased between 1 and 5 min of stenosis from 0.63 to 0.32 ml.min-1.g-1 in the outer layers (P less than 0.05) and from 0.26 to 0.15 ml.min-1.g-1 in the inner layers (P less than 0.05), despite constant hemodynamic conditions and pcor. Between 5 and 120 min of stenosis these values remained unchanged in the outer layers, but decreased further in the inner layers to 0.08 ml.min-1.g-1 (P less than 0.05). The accurate control of pcor, the reproducibility of the levels of residual blood flow and the ease of handling the stenosis system indicate that coronary artery stenosis controlled by perfusion pressure distal to the stenosis is a useful animal model to study events during regional myocardial ischemia. With the use of this model of low flow ischemia a biphasic increase of myocardial vascular resistance was observed, which is initiated during the first minutes of coronary artery stenosis.