LABORATORY INVESTIGATION VENTRICULAR PERFORMANCE Elfects of global ischemia on the diastolic properties of the left ventricle in the conscious dog

The alterations in regional diastolic mechanics that occur during regional myocardial ischemia (creep and increased myocardial stiffness) may be the result of interactions between the ischemic and surrounding nonischemic myocardium rather than the direct result of ischemia. Thus similar changes may not occur when the entire left ventricle is ischemic. To investigate this proposition, left ventricular diastolic mechanics were studied in seven chronically instrumented conscious dogs during global left ventricular ischemia. The anterior-posterior, septal-free wall, and base-apex axes of the left ventricle were measured with ultrasonic dimension transducers. Left and right ventricular pressures were measured with micromanometers. Myocardial blood flows were measured with left atrial injections of 15 gm radioactive microspheres. Global left ventricular ischemia was induced by hydraulic constriction of the left main coronary artery, which resulted in a 54% decrease in mean left ventricular subendocardial blood flow. Left ventricular volume, midwall circumference, and midwall circumferential stress were calculated from ellipsoidal shell theory. To construct pressure-strain and stress-strain relationships from diastolic data collected during vena caval occlusions, all measured and calculated dimensions were normalized to Lagrangian strains (fractional extension from unstressed dimension). During ischemia, creep (elongation of unstressed dimension) occurred in each of the three left ventricular axes. The mean unstressed dimension of the anterior-posterior axis increased from 5.39 + 0.53 to 5.85 -+0.50 cm (p ' .05); the septal-free wall unstressed dimension increased from 5. 11 +± 0.53 to 5.72 0.80 cm (p ' .05); and the base-apex unstressed dimension increased from 7.04 -+ 0.61 to 7.25 ± 0.65 cm (p < .05). The relationship between diastolic midwall circumferential stress and strain shifted upward and to the left with ischemia, indicating that an increase in intrinsic myocardial stiffness had occurred. As a result of these mechanical alterations, there was a decrease in left ventricular chamber compliance that was manifested by a leftward shift of the diastolic pressurevolume strain relationship. Neither systolic bulging nor dysynchronous systolic shortening occurred in any of the three left ventricular spatial axes during ischemia. Thus, during global left ventricular ischemia, changes in diastolic mechanics identical to those that occur during regional ischemia account for a loss of left ventricular chamber compliance. This suggests that although systolic dyskinesia during regional ischemia may result from interactions between areas of ischemic and nonischemic myocardium, changes in regional diastolic mechanics are the direct result of ischemia. Circulation 71, No. 3, 610-619, 1985. THE RESULTS of clinical and experimental studies have suggested that diastolic relationships between left ventricular pressure and dimension are altered by ischemia. Although the effects of ischemia on regional diastolic properties have been well documented, 1 2 less is known about the effects of global left ventricular From the Departments of Surgery and Medicine, University of Minnesota, Minneapolis. This work was supported by NIH grants HL-22152 and HL-20598 from the USPHS; NIH research fellowships HL-05704. HL-05759, HL06001, and HL-06143; and a grant from the American Heart Association, Minnesota Affiliate. Address for correspondence: Marc S. Visner, M.D., Box 312, Mayo Memorial Bldg., University of Minnesota Hospitals, Minneapolis. MN 55455. Received April 4, 1984: revision accepted Nov. 29, 1984. 610 ischemia on the diastolic pressure-volume relationship of the left ventricle. Data collected from patients with coronary artery disease3-9 have demonstrated that left ventricular end-diastolic pressure and volume both increase when there is an increased demand for cardiac output. Because left ventricular diastolic pressures at any given volume have been observed to be higher during ischemia, these data have been interpreted as demonstrating a decrease in the distensibility of the left ventricular chamber. Changes in the elastic properties of the myocardium, increases in right ventricular pressure, and incomplete ventricular relaxation are the most frequently invoked causes of this abnormality. On the other hand, there have been disparate results CIRCULATION by gest on Jne 6, 2017 http://ciajournals.org/ D ow nladed from LABORATORY INVESTIGATION-VENTRICULAR PERFORMANCE from experiments in animal preparations of global left ventricular ischemia. In dogs with coronary stenoses, left ventricular compliance has been shown to decrease during rapid atrial pacing.'0 Experiments in isolated heart preparations, however, have shown left ventricular compliance to be either unchanged" or increased'2 during acute global ischemia. The analysis of regional diastolic mechanics during regional left ventricular ischemia has emphasized the importance of characterizing the elasticity of the myocardium with rigorous mechanical theory and methodology.1"2 This type of methodology has not been used previously to analyze the changes in left ventricular compliance that occur during acute global left ventricular ischemia. The proper normalization of dimensions is essential if diastolic pressure-dimension data are to be interpreted meaningfully. When the resting or unstressed dimensions of an elastic material are variable, the analysis of elasticity must take into account this variability. As the left ventricle fills during diastole, changes in its dimensions must be referred to unstressed dimensions to determine to what extent the ventricle is being deformed from its unstressed configuration. One method of accomplishing this is to convert raw dimensions to Lagrangian strain, which is the fractional change in dimension from unstressed dimension. It has been shown that the unstressed dimension of myocardial segment length increases during regional ischemia (the creep phenomenon)." 2 For this reason, linear segments within ischemic regions become longer at any given left ventricular diastolic pressure. When myocardial segment length is not expressed as strain, regions of the left ventricle may appear to become more compliant rather than less compliant during ischemia. 1'-15 However, when segment length is properly normalized with respect to unstressed dimension, it has been observed that regions of the left ventricle actually become less compliant during ischemia.",2 If the same changes in myocardial mechanics that occur during left ventricular regional ischemia occur globally when the entire ventricle is ischemic, it would dictate that during global ischemia, pressure and dimension data must be analyzed with the same rigorous methodology previously used to analyze regional data. It would also suggest that the abnormalities that occur during regional ischemia are the direct result of ischemia rather than the result of interactions between the ischemic region and surrounding areas of nonischemic myocardium. The purpose of the present study was to examine the changes in diastolic mechanics that occur during global left ventricular ischemia induced by constriction of the left main coronary artery in the conVol. 71, No. 3, March 1985 scious dog. We also investigated to what extent altered myocardial elasticity, abnormal right ventricular loading, and prolonged left ventricular relaxation contribute to changes in left ventricular compliance during global ischemia. Materials and methods Experimental preparation. Seven healthy adult dogs (20 to 30 kg) were subjected to left thoracotomy under general anesthesia (30 mg/kg pentobarbital) for the implantation of instrumentation to collect ventricular pressure and dimension data (figure 1). The experimental preparation has been described previously. 16 In brief, three pairs of ultrasonic dimension transducers were implanted to measure the anterior-posterior minor axis, septal-free wall minor axis, and base-apex major axis of the left ventricle. The anterior-posterior and base-apex axes were measured as external diameters, with their respective transducers sewn to the left ventricular epicardium. The septalfree wall diameter was measured from the midwall of the interventricular septum to the epicardium of the lateral free wall. Silicone rubber catheters were implanted in the right ventricle and left atrium so that during subsequent studies, micromanometers could be introduced to measure right and left ventricular pressures. A third silicone rubber catheter, closed at its distal end by a compliant silicone rubber balloon (1/100 inch thickness), was positioned in the chest at the level of the aortic arch to measure intrapleural pressure. Bipolar pacing electrodes were sewn onto the right atrial appendage. Inflatable silicone rubber occluders were placed around the two venae cavae, and the azygos vein was ligated. A fluid-filled polyvinyl chloride catheter was inserted through the left internal mammary artery into the aortic arch to measure aortic pressure. A 6 mm inflatable silicone rubber occluder was positioned around the left main coronary artery. A 3.5 mm Statham electromagnetic flow probe was positioned around the anterior descending coronary artery proximal to its first major diagonal branch. The electrical leads, catheters, and occluders were all exteriorized dorsal to the thoracotomy incision. The pericardium was left open, and the chest was closed. Postoperatively the dogs received intramuscular injections of dihydrostreptomycin (0.75 g) and penicillin (6 x 105 U) for 3 days. Instrumentation and data acquisition. The dogs were allowed to recover from surgery for 7 days before they were studied. Data were collected while the dogs were awake and Vena Caval Occluder -