James D. Sink

Coronary Flow and Regional Function before and after Supraarterial Myotomy for Myocardial Bridging

Myocardial bridges have been associated with clinical and metabolic evidence of ischemia, although the mechanism for this is unclear. We measured coronary blood flow and segmental function at different heart rates prior to and after release of a myocardial bridge involving the left anterior descending coronary artery in a patient with angina. Before lysis of the bridge, atrial pacing was associated with a decreased systolic flow/total flow, increased duration of systole, a lag in diastolic flow, and functional deterioration. After release of the bridge, pacing was associated with increased systolic flow/total flow and systolic interval, no diastolic flow lag, and no functional deterioration. These data imply that before bridge division, systolic flow and the initiation of diastolic flow were impeded. Functional abnormalities resulting from the flow discrepancies at heart rates of 120 to 150 beats per minute may have accounted for this patients symptoms.

The Effects of Hypothermia on Myocardial Oxygen Consumption and Transmural Coronary Blood Flow in the Potassium-arrested Heart

Hypothermia remains the primary adjunct employed to lower cellular metabolism during various cardiac procedures. In these experiments, left ventricular myocardial oxygen consumption (MVO2) and transmural blood flow (TBF) were measured during cardiopulmonary bypass with the range of temperatures used clinically. Determinations were made in empty beating normothermic hearts and after potassium cardioplegia at 37, 32, 28, 22, 18, and 15° (K+ = 15–37 meq/L: Hct 25 volumes %). Oxygen content of the total coronary sinus collection was compared with a large volume arterial sample using a Lex-O2-Con-TL analyzer (vs Van Slyke, R = 0.98). Transmural blood flow was measured at each temperature using microspheres (8μ), and perfusion was maintained at 80 mmHg. Asystole (37°) alone decreased MVO2 from 5.18 ± 0.55 to 1.85 ± 0.20 ml O2/min/100 g of left ventricle or approximately 65% (p < 0.001). With progressive cooling to 15° an additional 82% decrement in oxygen uptake occurred during asystole (p < 0.001). During asystole at 37° the decrease in MVO2 was reflected mainly by a large decrement (p < 0.01) in TBF (1.27 ± 0.19 to 0.74 ± 0.17 ml/min/g of mean left ventricular flow). However, with cooling below 32°, the arteriovenous oxygen difference narrowed progressively (p < 0.001) while TBF paradoxically returned to control levels. Endocardial/epicardial flow ratios were not altered by cooling. These data not only confirm earlier reports describing a sequential drop in MVO2 with incremental myocardial cooling, but also establish MVO2 levels for perfused hearts arrested by potassium at lower temperatures (18–15°). Moreover, as transmural blood flow becomes independent of metabolic necessity during hypothermia, coronary autoregulation appears to be impaired, possibly affecting detrimental tissue over perfusion.

The coronary pressure-flow determinants left ventricular compliance in dogs.

Displacement of the left ventricular diastolic pressure-dimension relationship (change in compliance) has been observed with alterations in coronary perfusion pressure. The relative contribution of coronary (myocardial) blood flow, as compared with the perfusion pressure at which flow occurs, was studied in 10 dogs during diastolic relaxation by potassium arrest during cardiopulmonary bypass. The normalized left ventricular pressure-dimension relationships, obtained during passive, gradual filling of the left ventricle (0–20 mm Hg) were shifted progressively to the left as coronary perfusion pressure was Increased. Myocardial blood flow was 0.06 ml/mg per min ± 0.02 ml/mg per min (mean ± SEM) at a coronary perfusion pressure of 40 mm Hg and increased to 0.38 ml/mg per min ± 0.11 ml/mg per min as the coronary perfusion pressure was raised to 120 mm Hg. Addition of adenosine significantly Increased myocardial blood flow by 109% at a coronary perfusion pressure of 80 and by 147% at a coronary perfusion pressure of 120 mm Hg, but caused no additional significant shifts in the pressure-dimension relationships, compared to the same coronary perfusion pressures without adenosine. Coronary perfusion pressure, and not coronary blood flow, is a more direct determinant of cardiac diastolic properties.

Comparison of Nonpulsatile and Pulsatile Extracorporeal Circulation on Renal Cortical Blood Flow

Radioactive microspheres were used to compare renal cortical blood flow with pulsatile and nonpulsatile extracorporeal perfusion in mongrel dogs. No difference was found in total renal cortical flow or in flow distribution using pulsatile compared with nonpulsatile perfusion when mean perfusion pressure was held constant at a high (80 mm Hg) or low (50 mm Hg) level. Although the present investigation does not resolve the question of whether pulsatile perfusion has advantages over nonpulsatile perfusion in maintaining renal function, the data indicate that any differences between the two techniques must be explained by a mechanism other than increased total cortical blood flow or by redistribution of cortical flow.

An Improved Technique for Producing Ventricular Hypertrophy with a Subcoronary Valvular Aortic Stenosis Model

Although techniques for producing aortic valve stenosis proximal to the ostia of the coronary arteries have been described in experimental animals, only moderate left ventricular hypertrophy has been obtained. A technique for plicating the noncoronary sinus of Valsalva in puppies is presented that has enabled us to achieve levels of ventricular hypertrophy not previously reported with methods for subcoronary aortic stenosis.

Protection of mitochondrial function during ischemia by potassium cardioplegia: correlation with ischemic contracture.

The effect of potassium cardioplegia on mitochondrial function was evaluated in the ischemic isolated rat heart. Mitochondrial function as well as adenosine triphosphate (ATP) levels were determined at the initiation of ischemic contracture, at the completion of ischemic contracture, and 20 minutes following contracture completion. Group I received no cardioplegia prior to ischemia, while Group II received potassium cardioplegia prior to the onset of ischemia. The respiratory control index (RCI), which is the primary measure of the intactness of mitochondrial function, was calculated with both a NAD (nicotinamide adenine dinucleotide)-linked substrate and a FAD (flavin adenine dinucleotide)-linked substrate. Potassium cardioplegia significantly delayed ischemic contracture initiation and completion. Although the RCI and ATP levels decreased significantly at successive levels of contracture, there was no difference in the RCI or ATP content between Group I and Group II at contracture initiation or completion. Unlike previous investigations that have used a time-base to examine mitochondrial function and acute cardiac ischemic injury, we correlated mitochondrial function with the measurable physiologic event ischemic contracture. The data indicated that potassium cardioplegia preserved ATP content and mitochondrial function, and that contracture initiation and completion correlate well with specific ATP levels and mitochondrial respiratory control. The relationship between mitochondrial function and ATP content indicates that the beneficial effect of potassium cardioplegia on mitochondrial function may be secondary to the preservation of high-energy phosphate levels which provide energy for mitochondrial maintenance.

Myocardial Blood Flow and Oxygen Consumption in the Empty-Beating, Fibrillating, and Potassium-Arrested Hypertrophied Canine Heart

Myocardial oxygen consumption and blood flow distribution were examined in severely hypertrophied canine hearts in the empty-beating, fibrillating, and pharmacologically arrested states. Hypertrophy was produced using a subcoronary valvular aortic stenosis model that mimics the clinical situation of aortic valvular stenosis. Oxygen content of the total coronary sinus collection was compared with a large volume arterial sample using a Lex-O2-Con-TL analyzer, which had been validated by the Van Slyke-Neill method. Transmural blood flow was measured in each state using microspheres, and perfusion pressure was maintained at 80 mm Hg. Oxygen consumption in the empty-beating hypertrophied heart was found to be the same as that previously reported for normal hearts. Blood flow was evenly distributed in the empty-beating heart, with an endocardial/epicardial ratio of 0.99 +/- 0.15 (SEM) milliliters per minute per gram of left ventricular weight. Oxygen consumption failed to increase significantly with fibrillation; however, blood flow distribution favored the subepicardium, suggesting that oxygen consumption determinations in the fibrillating hypertrophied heart may not accurately reflect metabolic demand. Basal oxygen consumption of the hypertrophied heart as determined by the potassium-arrested, blood-perfused model was the same as that previously described for normal hearts. Blood flow during potassium arrest favored the subendocardium (endocardial/epicardial ratio = 1.14 +/- 0.27 ml/min/gm LV weight).

Effect of B-15,000 (Iopamidol), A New Nonionic Contrast Agent, on Cardiac Function of the Isolated Rat Heart

The isolated rat heart model was used to examine the effect of a new nonionic contrast agent, B-15,000 (Iopamidol), on cardiac function. Comparative studies were performed with Amipaque, Renografin 60, Renografin 76, and Vascoray. The three ionic contrast agents had significantly greater detrimental effects on cardiac function than either nonionic agent. The results support the continued evaluation of the nonionic agents for use in coronary angiography.

The comparative effects of pulsatile and nonpulsatile myocardial perfusion during cardiopulmonary bypass

Abstract The salutary effects of pulsatile perfusion (P) during clinical cardiopulmonary bypass (CPB) remain controversial. The notion exists that coronary blood flow may be enhanced by P, especially when a significant coronary stenosis occurs. In this study pressure-flow characteristics were assessed during CPB with and without P in 13 fibrillating dog hearts (37°C). Radionuclide microspheres measured transmural blood flow in normal myocardium (NR) and in regions supplied by collateral coronary arteries (CR) which restrict blood inflow at mean pump pressures of 80 and 50 mm Hg during either P or nonpulsatile perfusion (NP). Retrograde circumflex pressure (RC P ) also served as an index of CR perfusion. At both pressures, mean myocardial blood flow to both NR and CR was not augmented by P despite aortic pulse pressures of approximately 50 mm Hg. Moreover, endocardial/epicardial flow ratios were unchanged from control in both regions after beginning pulsatile flow. At the same time, the mean RCP in CR was not affected by P even though a pulsatile pattern was transmitted across the collateral bed. Thus, the most significant factors affecting transmural blood flow during pulsatile CPB appear to be the coronary perfusion pressure and degree of inflow limitation, not the perfusion wave form. Therefore, any benefits which might be associated with clinical pulsatile perfusion during CPB appear to result from factors other than coronary blood flow augmentation.

The relationship of transmural myocardial blood flow to midwall function

Abstract The relationship of transmural myocardial blood flow to midwall function was evaluated in seven adult mongrel dogs anesthetized with morphine SO4 (3 mg/kg) and a-chloralose (80 mg/kg) and instrumented with catheters for measuring aortic and left ventricular end-diastolic pressures and dp/dt. Three pairs of miniature ultrasonic transducers (3 mm diameter) were positioned at midwall level of the left ventricle along the minor axis within each of the three regions: anterior, lateral, and posterior segments. Transmural blood flow in the epicardium and endocardium was measured utilizing 8- to 10-μm tracer microspheres before and after a 60-sec circumflex occlusion. Functional data for extent (ΔL) and rate (dl/dt) of systolic shortening were determined and systolic excursion was normalized to an initial end-diastolic length of 10 mm. Total circumflex occlusion for 1 min was associated with a severe flow imbalance to the posterior endocardium (endocardium/epicardium 0.2 ± 0.1) resulting in marked functional impairment (ΔL = -0.5 ± 0.2 mm, dl/dt = -1.6 ± 1.1 mm/sec) and holosystolic bulging. Flow within the lateral region was not as severely impaired (endocardium/epicardium 0.5 ± 0.1, P