Ascending aortic aneurysm and dissection in young adults with bicuspid aortic valve: implications for echocardiographic surveillance.

Bicuspid aortic valve (BAV) is an independent risk factor for aneurysm and dissection of the ascending aorta. Despite this association, routine imaging of the aorta has not been recommended for patients with BAV. We describe two young men who developed life-threatening aneurysm or dissection of the ascending aorta; one had a normally functioning BAV and the other was 10 years after valve replacement. The pathology of this condition is very similar to that found in the Marfan syndrome. We recommend echocardiographic surveillance of the ascending aorta at regular intervals, and consideration of beta-adrenergic blockade among patients with significant dilation.

Prospective, randomized clinical study of ischemic preconditioning as an adjunct to intermittent cold blood cardioplegia.

BACKGROUND: Ischemic preconditioning has been shown to be beneficial to myocardial preservation in a variety of models. This study was performed to determine whether ischemic preconditioning can ameliorate the postischemic myocardial dysfunction often seen in patients undergoing open heart operations. METHODS: Seventy patients were prospectively randomized to receive or not receive ischemic preconditioning before intermittent cold blood cardioplegic arrest. Ischemic preconditioning was induced by 1 minute of aortic cross-clamping followed by 5 minutes of reperfusion during normothermic cardiopulmonary bypass, immediately before cardioplegic arrest. Control patients had an extra 6 minutes of normothermic cardiopulmonary bypass before cardioplegic arrest. Hemodynamic parameters were obtained before bypass, and at 1, 6, and 12 hours after weaning from bypass. All patients were monitored for the development of postoperative complications and need for inotropic agents or intraaortic balloon pumping. RESULTS: Preconditioned patients showed marked improvement in cardiac index from a preoperative value of 2.2 +/- 0.1 L x min(-1) x m(-2) to 2.5 +/- 0.1 L x min(-1) x m(-2) at 1 hour after bypass (p < 0.01), 2.8 +/- 0.1 L x min(-1) x m(-2) at 6 hours after bypass (p < 0.0001), and 2.9 +/- 0.1 L x min(-1) x m(-2) at 12 hours after bypass (p < 0.0001). In the control group the cardiac index deteriorated significantly from 2.5 +/- 0.1 to 2.2 +/- 0.1 L x min(-1) x m(-2) at 1 hour after bypass (p < 0.05), and then only returned to baseline at 6 and 12 hours after bypass. Thirteen control patients required inotropic agents; however, none of the ischemic preconditioning group required inotropic agents (p < 0.001). There was no significant difference between the groups with respect to postoperative morbidity and mortality. CONCLUSIONS: Ischemic preconditioning significantly improves heart function in clinical cardiac operations, decreases the need for inotropic support, and could be an important adjunct to myoprotective strategies.

Recovery of nonbeating donor hearts.

BACKGROUND: Use of hearts from non-heart-beating donors could greatly increase the pool of cardiac homografts. This hypothesis was investigated in a model of traumatic death with New Zealand rabbits which were exsanguinated after 10 minutes of hypotension. METHODS: The hearts were left in situ at normothermia until just before the onset of contracture, were surgically exposed, given either blood cardioplegic, crystalloid cardioplegic, or University of Wisconsin cardioplegic solution, and then stored for 1 hour at 4 degrees C in the respective solutions. The hearts were reperfused for 20 minutes with a Langendorff apparatus. A balloon was placed in the left ventricle, and peak developed pressure and diastolic pressure-volume relationship data were collected over a range of balloon volumes. Control data was obtained from nonischemic rabbit hearts. RESULTS: Blood cardioplegic solution preserved peak developed pressure and the slope of diastolic pressure-volume relationship at control levels, whereas crystalloid cardioplegic and University of Wisconsin solutions showed significant deterioration in both of these indexes. The total adenine nucleotide pool was significantly improved with the use of blood cardioplegic solution compared with crystalloid cardioplegic and University of Wisconsin solutions although all groups were significantly depressed compared with control values. CONCLUSIONS: This study indicates that hearts harvested from non-heart-beating donors can have function that is not statistically different from controls if preserved with blood cardioplegic solution and that University of Wisconsin and crystalloid cardioplegic solutions are inadequate for preserving hearts harvested under these unique conditions.

Ischemic preconditioning improves preservation with crystalloid cardioplegia.

Ischemic preconditioning has not been investigated in a clinically relevant model of hypothermic multidose cardioplegia arrest. Using isolated rabbit hearts perfused on a Langendorff apparatus, ischemic preconditioning was investigated as an adjunct to crystalloid cardioplegia during a 2.5-hour ischemic period at 15 degrees C. After baseline functional data were obtained, ischemic preconditioning was induced with either 1 minute or 5 minutes of normothermic ischemia, followed by 5 minutes of reperfusion before the arrest period. Control hearts underwent no ischemic preconditioning. The control hearts exhibited a decrement in both the peak developed pressure and diastolic function, as measured by the slope of the diastolic pressure-volume relationship, of from 107 +/- 2 to 68 +/- 7 mm Hg (p < 0.005) and from 0.99 +/- 0.2 to 2.95 +/- 0.44 mm Hg/0.1 mL (p < 0.005), respectively. Hearts exposed to either 1 or 5 minutes of normothermic ischemia showed no significant change in the slope of the diastolic pressure-volume relationship. Hearts exposed to 1 or 5 minutes of normothermic ischemia also had a significant decrease in the peak developed pressure of from 107 +/- 6 to 92 +/- 2 mm Hg and from 102 +/- 3 to 85 +/- 4 mm Hg, respectively (p < 0.05). However, ischemic preconditioning brought about a significant improvement in the postischemic peak developed pressure, as opposed to that seen for the control hearts (p < 0.05). Creatine kinase washout was significantly higher in the control hearts only. High-energy phosphate levels, lactate levels, the percentage wet weight, and tissue creatine phosphate levels were not significantly different among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The efficacy of blood cardioplegia is not due to oxygen delivery.

Twenty-seven canine hearts instrumented with ultrasonic dimension crystals underwent simultaneous determination of stroke work and myocardial oxygen consumption during incremental volume loading on right heart bypass before and 30 minutes after 2 hours of cardioplegic arrest at 10 degrees C. Three cardioplegic solutions were used: Hematocrit values were 17.0% (group I), 8.2% (group II), and 0% (group III). In all groups the slope of the linear stroke work versus end-diastolic volume relationship, a measure of contractility, was unchanged after ischemic arrest. However, the myocardial oxygen consumption for basal metabolism was increased an average of 25.5% after arrest with plasma (group III). Since the plasma concentration in all three groups was identical, and the oxygen available to the hearts during ischemia was the same in groups II and III, the efficacy of blood-based cardioplegic solutions cannot be attributed to a plasma component or to the greater oxygen-carrying capacity of the red blood cell. Future studies should attempt to identify the salutory entity of the red cell responsible for preservation of myocardial oxygen consumption efficiency.

Amelioration of postischemic stunning by deferoxamine-blood cardioplegia.

Limitation of oxygen free-radical injury was assessed in canine hearts by sonomicrometrically quantifying regional stroke work (RSW) in areas of myocardium perfused by the left anterior descending (LAD) and left circumflex (LCX) arteries. Volume loading of the left ventricle was performed on modified right-heart bypass before and 30 minutes after 20 minutes of LAD occlusion followed by 60 minutes of global cardioplegic arrest with either blood cardioplegia (group 1), blood cardioplegia with adjuvant deferoxamine (500 mg/l) plus 100 mg infused into the aortic root for 5 minutes after unclamping (group 2), or blood cardioplegia with adjuvant deferoxamine (600 mg/l) with unmodified reperfusion (group 3). Surgical revascularization was modeled by reopening the LAD with the first cardioplegia reinfusion. The slope of the RSW versus preload relation (a load-independent index of contractility) was decreased by a mean amount of 44% in the LAD region of group 1 hearts but was preserved in group 2 and 3 hearts. The slope of the LCX region was preserved in all groups. The use of adjuvant deferoxamine in this model of early surgical reperfusion eliminates measurable postischemic stunning.

Assessment of the intrinsic contractile state within an area of myocardium.

Afterload independent, inotropic state sensitive indices of regional function were sought in 31 canine hearts instrumented with piezoelectric crystals to depict trapezoidal areas in the left anterior descending and circumflex arterial beds. Control and postinterventional end-systolic pressure versus regional length and area relationships and regional stroke work versus end-diastolic length and area relationships were inscribed during incremental volume loading on right heart bypass. Hearts were randomized to undergo afterload variation with phenylephrine infusion, contractility augmentation by calcium chloride, or 20 minutes of ischemia in the region of the left anterior descending artery with 30 minutes of reperfusion. All relationships were linear before and after each intervention (mean r = 0.726 to 0.974). The slopes of each correlation were interpreted to quantify intrinsic regional contractility, and all were afterload insensitive (unaffected by phenylephrine). Regional stroke work versus end-diastolic area and length relationships were depressed 55% and 62%, respectively, after ischemia (p less than 0.001 each), whereas neither end-systolic pressure versus regional area nor regional length was significantly altered. Calcium chloride increased regional stroke work versus area 45% in both arterial beds, but significantly increased the other indices only in the left anterior descending and not the left circumflex region. Unlike previous studies of global contractility, correlation of end-systolic events alone did not reliably discriminate perturbations in regional function. The superiority of regional stroke work versus end-diastolic area may be due to incorporating pressure-area changes during the entire cardiac cycle and obviating variability owing to crystal orientation inexactly parallel to fiber shortening.

Maturational difference in functional/metabolic sequelae of free radical formation on reperfusion.

To detect maturational differences with ischemia/reperfusion injury on cardiac metabolism and function, isolated nonworking rabbit hearts were subjected to 30 min of 37 degrees C ischemic arrest and reperfusion. Pre- and postischemic high energy phosphate contents (ATP, ADP, AMP), conjugated diene (products of free radical mediated lipid peroxidation) production, and peak isovolumic developed pressure (PDP) were measured in newborn (3-5 days, n = 8), 2- to 3-week-old (n = 8), and adult (2-4 months, n = 8) rabbits. ATP content decreased significantly during ischemia in all three age groups but recovered significantly toward preischemic levels in the newborn and 2-week-old groups but not in adult animals. AMP was much better preserved in the two younger groups with significantly higher levels at end-ischemia. Conjugated dienes were present in newborn and adult heart in small amounts at preischemia and rose slightly by end-ischemia. Newborn hearts accumulated large amounts of dienes by 10 min of reperfusion, which were significantly greater than those adult hearts. PDP returned to 85 and 91% of control in newborn and 2-week-old hearts, respectively, and to only 66% of control in adult hearts (P less than 0.05). These data suggest that the postischemic immature heart recovers energy stores and ventricular function faster than the adult heart which can be attributed to preservation of the total adenine nucleotide pool during ischemia. This improved recovery occurs despite a greater amount of free radical-mediated lipid peroxidation with reperfusion in newborn hearts.

Upgrading acellular to sanguineous cardioplegic efficacy.

To determine which biochemical entity of the red cell is responsible for preventing augmented postischemic myocardial oxygen consumption (MVO2), 28 canine hearts instrumented with ultrasonic dimension crystals underwent simultaneous determination of stroke work (SW) and MVO2 during incremental volume loading on right heart bypass before and 30 min after 2 hr of 10 degrees C cardioplegic arrest with unmodified oxygenated crystalloid cardioplegia (OC), OC with histidine of equal buffering capacity as 18% hematocrit blood (OC + H), or OC with 200 units/ml of superoxide dismutase and catalase (OC + SOD/C). In all groups, the slope of the linear SW vs end-diastolic volume relationship, Mw, and the slope of the linear SW vs MVO2 relationship, Me, were unchanged after cardioplegic arrest. The intercept of the SW vs MVO2 relationship, Eo, was augmented an average of 22.2% in the OC group, but both OC + H and OC + SOD/C prevented this subtle expression of ischemic injury. The characteristic of the red cell most likely responsible for the myoprotective efficacy of blood cardioplegia is buffering capacity; however, since the effects of tissue acidosis are partially mediated by free radicals, the use of free radical scavengers can also ameliorate ischemic damage incurred during cardioplegic arrest.

Review of invasive treatments of coronary artery disease.

Coronary artery disease is a difficult clinical entity to manage, and all forms of current therapy are palliative in nature. Results from the large randomized studies have clearly demonstrated the superiority of surgical versus medical therapy in subsets of patients previously described herein. As patients with severely compromised ventricles are demonstrated to fare better with bypass procedures, the number of patients that should be operated upon continues to grow. With refinements in operative and perioperative care and increased use of the internal mammary artery as the bypass conduit, it is inevitable that more subgroups will be determined to be best managed by surgical revascularization. For the present time, medical treatment is preferred for the vast majority of patients who were shown by randomized trials not to benefit significantly from surgical intervention. However, caution must be used in excluding patients based on trial results that used surgical techniques and conduits that are ten years old. The role of angioplasty in the invasive treatment of ischemic cardiac disease is still in evolution. Although not yet proved by vigorous trials, it is a procedure that most likely will continue to be used in many clinical applications. The high rate of restenosis after angioplasty, which is a formidable problem, may be a factor that will limit the application of angioplasty to patients with acute myocardial infarction or to those who do not desire surgical intervention. The answers to these and other complex problems of patient management must await well-designed prospective trials comparing angioplastic with surgical revascularization. Clinical use of some of the experimental procedures mentioned is certain; the efficacy and role of these procedures in the treatment of ischemic cardiac disease must also be defined with future studies.

The conundrum of the effect of beta-blockade on myocardial oxygen consumption.

The effect of propranolol on myocardial oxygen consumption was studied in in situ canine hearts. In 12 afterload independent isovolumic hearts propranolol increased MVO2 an average of 19 +/- 3% (P less than 0.01) for all peaked developed pressure intervals from 75 to 175 mm Hg, secondary to increased wall stress. In 10 hearts instrumented for computer acquisition of pressure-volume workloops during progressive volume loading on right heart bypass, propranolol decreased preload recruitable stroke work an average of 36% (P less than 0.05). However, propranolol failed to decrease the amount of oxygen consumed for basal metabolism or external mechanical work when MVO2 is indexed for heart rate, heart weight, and stroke work. Therefore, propranolol does not decrease MVO2 for individual contractions and does not affect the energy requirements for basal metabolism, excitation-contraction coupling, and heat generation, in contrast to results obtained with beta agonists.

A review of the tumors of the salivary gland.

Neoplasms of the salivary gland are an interesting, diverse group of tumors with many associated factors, which make them a therapeutic challenge. Their long natural history, the wide spectrum of biologic activity which they exhibit, the difficulty in diagnosis and their high rate of recurrence contribute to the complexity of their management. Operation is the principle method of treatment for these tumors, but radiation therapy plays a significant role in the control and palliation of malignant tumors of the salivary gland. It is the hope for the future that effective chemotherapy agents will contribute significantly to the treatment of malignant tumors of the salivary gland.