Removal of splenic cyst with salvage of functional splenic tissue.
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Child↗
Biomedical subjects
J D Sink
Publications and source records attributed to J D Sink.
Depressed high-energy phosphate content in hypertrophied ventricles of animal and man: the biologic basis for increased sensitivity to ischemic injury.
It is frequently stated that hypertrophied ventricles tolerate ischemia less well than nonhypertrophied ventricles. The authors' earlier studies in a rat supravalvular aortic stenosis model and canine valvular aortic stenosis model, both with concentric left ventricular hypertrophy, disclosed accelerated rates of ischemic contracture and diminished basal myocardial high energy phosphate stores. These studies have been extended to ten patients with severe left ventricular hypertrophy caused by valvular aortic stenosis and normal coronary arteries. ATP (endocardial and epicardial) from transmural left ventricular biopsies taken at operation before aorta cross-clamping, and frozen immediately in liquid nitrogen, were compared with similar biopsies from patients with nonhypertrophied myocardium supplied by normal coronary arteries. The subendocardial high energy phosphate levels in the nonhypertrophied myocardium was greater than high energy phosphate levels in the subepicardium of nonhypertrophied ventricles (ATP-micromoles/gram-protein, epi = 36.8 +/- 3.3, endo = 37.7 +/- 3.3) (p = NS). However, in the hypertrophied myocardium the subendocardium consistently showed significantly depressed high-energy phosphate levels when compared with subepicardial levels (ATP-hypertrophied myocardium, epi = 31.5 +/- 1.6, endo = 25.9 +/- 1.7) (p less than 0.05). This uniform depression of ATP stores, greatest in the subendocardium, in left ventricular hypertrophy suggests a common biologic mechanism for the enhanced sensitivity to ischemia. Of importance for patients may be the prior observation in rats that repletion of ATP( stores before ischemia eliminates the accelerated rate to ischemic contracture. Diminished subendocardial ATP stores appear to be an intrinsic property of severely hypertrophied myocardium and probably contribute to its enhanced sensitivity to ischemia.
Adenine Nucleotides↗
Improved tolerance to ischemia in hypertrophied myocardium by preischemic enhancement of adenosine triphosphate.
In prior studies from this laboratory to determine the mechanisms whereby hypertrophied myocardium is more sensitive to ischemic injury than normal myocardium, it was demonstrated that hypertrophied rat hearts have lower basal high-energy phosphate levels and develop ischemic contracture sooner than normal myocardium. The purposes of this study were (1) to determine if the decrease in myocardial adenosine triphosphate (ATP) was associated with the increased rate of ischemic contracture and (2) to determine if arrest and perfusion of hypertrophied myocardium prior to the ischemic interval would allow recovery of high-energy phosphate stores and improve tolerance to ischemia. ATP levels were measured in isolated normal and hypertrophied rat hearts during (1) control nonworking Langendorff perfusion, (2)2 minutes of potassium chloride-arrested perfusion (30 mEq/L), or (3) 15 minutes of potassium chloride-arrested perfusion (30 mEq/L). Both groups were then made globally ischemic (37 degrees C) and the time to ischemic contracture recorded. Hypertrophied hearts were produced by permanent banding of the ascending aorta and confirmed by left ventricular (mg) body weight (gm) ratios (normal, 1.95 wet, p less than 0.05). After 2 minutes of mechanical arrest the time to ischemic contracture was increased 75% +/- 10% in normal and 44% +/- 4% in hypertrophied hearts. After 15 minutes of mechanical arrest with perfusion, hypertrophied myocardium re-established normal ATP levels and increased its time to ischemic contracture by 130% +/- 7%. These studies suggest that during potassium chloride arrest, additional preischemic metabolic recovery is possible by hypertrophied myocardium and leads to increased tolerance to ischemia beyond that accomplished by cessation of mechanical activity alone. This effect is seen only to a minor degree in normal myocardium.
Adenosine Triphosphate↗
The comparative effects of pulsatile and nonpulsatile myocardial perfusion during cardiopulmonary bypass.
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Animals↗
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 patient's symptoms.
Adult↗
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 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.
Adenosine↗
Characteristics of chronic left ventricular hypertrophy induced by subcoronary valvular aortic stenosis. I. Myocardial blood flow and metabolism.
Using a canine model of subcoronary valvular aortic stenosis, we determined myocardial blood flow, high-energy phosphate content, and mitochondrial function in eight hearts with chronic left ventricular hypertrophy. Fourteen normal hearts were used for control data. Myocardial blood flow was determined by injection of tracer microspheres. During cardiopulmonary bypass, left ventricular transmural biopsy specimens were taken for metabolic analyses. Subepicardial and subendocardial content of adenosine triphosphate (ATP) and creatine phosphate (CP) were assayed. Respiratory control indices for isolated mitochondria were measured by use of NAD-linked and FAD-linked substrates. Endocardial blood flow, subendocardial high-energy phosphate content, and respiratory control indices for NAD-linked substrate in the hearts with chronic left ventricular hypertrophy were significantly lower than the normal values. These data provide insight into the metabolic and myocardial blood flow abnormalities occurring in cardiac hypertrophy and provide a framework for understanding the altered response of hypertrophied hearts to ischemia.
Adenosine Triphosphate↗
Characteristics of chronic left ventricular hypertrophy induced by subcoronary valvular aortic stenosis. II. Response to ischemia.
The increased susceptibility of hearts with chronic left ventricular hypertrophy (CLVH) to damage during ischemia has been suggested but not documented. The purpose of this study was to isolate ischemic events in hearts with CLVH from reperfusion events. Using physiological and biochemical parameters, we compared the rate and extent of myocardial injury during ischemic contracture between eight canine hearts with CLVH induced by subcoronary valvular aortic stenosis and 14 normal canine hearts. Preischemic myocardial blood flow was determined by injection of tracer microspheres. During cardiopulmonary bypass, each heart was instrumented with a left ventricular balloon and made globally ischemic. At control, contracture initiation, and contracture completion left ventricular transmural biopsy specimens were assayed for subepicardial and subendocardial adenosine triphosphate (ATP) and creatine phosphate (CP). Mitochondrial respiratory control indices for NAD-linked and FAD-linked substrates were measured. Preischemic endocardial blood flow in hearts with CLVH was significantly lower than in normal hearts. At control, subendocardial ATP and CP and the respiratory control index for NAD-linked substrate were significantly lower in hearts with CLVH than in normal hearts. Hearts with CLVH reached contracture initiation significantly sooner than normal hearts. All hearts demonstrated significant decreases in high-energy phosphate content and mitochondrial function during ischemia. Reperfusion injury notwithstanding, we concluded that hearts wih CLVH are more susceptible to ischemic injury than are normal hearts, perhaps related to lower endocardial blood flow, lower subendocardial high-energy phosphate stores, and depressed mitochondrial function prior to ischemia.
Adenosine Triphosphate↗
Response of hypertrophied myocardium to ischemia: correlation with biochemical and physiological parameters.
The increased susceptibility of hypertrophied hearts to ischemic injury during cardiac operations has long been recognized. Although the imbalances in oxygen supply and demand which may occur with hypertrophy during hypotension, ventricular fibrillation, or reperfusion have been extensively studied, the biochemical response of hypertrophied myocardium to ischemia has not been fully elucidated. In the present investigation, rat hearts in which hypertrophy was induced by chronic pressure overload were used to examine the relationship of the physiological parameter, ischemic contracture, to high-energy phosphate content and mitochondrial function during global ischemia. Hypertrophied hearts developed ischemic contracture after significantly shorter duration of ischemia than did normal hearts (5.8 +/- 0.3 minutes versus 10.1 +/- 0.7 minutes). High-energy phosphate content was lower in hypertrophied hearts at control and at ischemic contracture initiation and completion than in normal hearts, whereas mitochondrial function was consistently greater in the hypertrophy group. This investigation demonstrates that the hypertrophied myocardium, independent of flow-related events, is more vulnerable to ischemic injury than normal myocardium and suggests that the increased susceptibility may result from lower high-energy phosphate stores present at the onset of ischemia. The results emphasize the need for rapid cardiac arrest with the induction of ischemia in hypertrophied myocardium and suggest the potential for increasing myocardial high-energy phosphate content in the hypertrophied ventricle by interventions such as arrested perfusion with substrate containing oxygenated cardioplegic solutions prior to the onset of planned ischemia.
Animals↗
Pulmonary resection in the management of metastases from gestational choriocarcinoma.
Case histories of five patients with pulmonary metastases from choriocarcinoma resistant to multidrug chemotherapy are presented. Thoracotomy was performed in all cases. All tumor was removed in three patients with no other site of active disease, and these patients are surviving with no evidence of recurrent disease. In one patient, the lesion could not be completely excised because of involvement of contiguous structures, and she died of progressive disease. A second patient, with liver metastases at the time of thoracotomy, also died of progressive disease. The indications for performing thoracotomy in the management of pulmonary metastases of choriocarcinoma are discussed.
Adult↗
Metabolic deterioration during global ischemia as a function of time in the intact normal dog heart.
High-energy phosphate content and mitochondrial function were analyzed at the initiation and completion of ischemic contracture in dog hearts exposed to normothermic ischemia while on cardiopulmonary bypass. Contracture initiation and completion were detected by a balloon catheter placed within the left ventricle. In seven dogs, inner and outer layers of the myocardium were assayed for adenosine triphosphate (ATP) and creatine phosphate (CP). ATP and CP content in these two layers were compared prior to ischemia and at contracture initiation and completion. Inner layer ATP levels were 23.88 +/- 0.73 (mean +/- SM) mu moles/gm dry weight prior to ischemia, 5.14 +/- 0.49 at initiation, and 0.73 +/- 0.2 at completion. Inner layer CP content was 41.29 +/- 0.87 prior to ischemia, 3.49 +/- 0.34 at initiation, and 4.06 +/- 0.48 at completion. Mitochondrial respiratory control indices (RCI) were assayed in a second group of seven dogs prior to ischemia, at contracture initiation, and at contracture completion and were, respectively, 11.5 +/- 1.18, 3.1 +/- 0.43 and 1.76 +/- 0.29 (alpha ketoglutarate as substrate). Despite the specific degrees of metabolic deterioration associated with the events of contracture, ischemic time required to develop contracture initiation and completion was variable, ranging from 29.5 to 72 minutes for initiation and 60.25 to 101 minutes for completion. A third group of five dogs had biopsy specimens taken for ATP at fixed ischemic time intervals, and at 45 minutes of ischemia they were found to have greater ranges in ATP values than the ranges associated with contracture initiation. In contrast to ischemic time, the physiological events of ischemic contracture are reliable predictors of the degree of metabolic injury in the intact dog heart exposed to normothermic ischemic arrest during cardiopulmonary bypass.
Adenosine Triphosphate↗
Perioperative assessment of segmental left ventricular function in man. Effects of nitroprusside after bypass operations.
Direct on-line assessment of postoperative ventricular function has not been possible. We assessed the feasibility of using pulse-transit sonomicrometry to measure regional function in man postoperatively. Ultrasonic transducers (3 mm in diameter) were implanted along the minor axis of the left ventricle at midwall depth into a region supplied by a bypass graft. All wires were tunneled subcutaneously. Pressures, ECG, and regional dimensions were monitored in eight patients continuously, and at 48 to 72 hours postoperatively, the effects of sodium nitroprusside were assessed. The transducers were withdrawn with no complications. Nitroprusside was associated with an increase in systolic shortening from 1.60 +/- 0.19 to 1.92 +/- 0.25 mm and rate of shortening from 12.13 +/- 1.85 to 15.34 +/- 2.38 mm/s at constant end-diastolic lengths. Using this technique for recording regional dimensions, nitroprusside therapy augmented function at a constant preload.
Adult↗
The relationship of transmural myocardial blood flow to midwall function.
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Animals↗
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.
Animals↗
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.
Animals↗
Primary intracranial melanoma presenting as a suprasellar tumor.
A 37-year-old white woman presented with progressive visual loss in the right eye. The diagnostic evaluation suggested a tumor in the suprasellar area. At operation an isolated melanoma was found just superior to the sella turcica. No evidence of other intracranial lesions was present and complete diagnostic studies failed to reveal any other primary site. The patient subsequently underwent a second neurosurgical procedure in an effort to remove the tumor completely. This was followed by recurrent symptomatology and she was then treated with a combination of multiple drug chemotherapy and immunotherapy. Approximately 3 years after her initial operation the patient succumbed secondary to her disease. The autopsy findings were consistent with a primary melanoma of the leptomeninges in the area just above the sella turcica. This unusual presentation is discussed and plausible hypotheses are given.
Adult↗
Correlation of mitochondrial function and ischemic contracture.
Structural and functional changes in the mitochondrium have been described following timed cardiac ischemia. However, mitochondrial abnormalities associated with acute muscular dysfunction have not been well defined. In the present investigation, the isolated rat heart subjected to global ischemia was used to determine the relationship between the biochemical parameters of high-energy phosphate content and mitochondrial function and the physiological event of ischemic contracture. High-energy phosphate content and mitochondrial structure and function were determined under control conditions, at the initiation of ischemic contracture, at the completion of ischemic contracture, and 20 minutes after completion of contracture. Contracture initiation and completion were associated with the anticipated depletion of high-energy phosphate content. Also demonstrated were specific degrees of structural and functional deterioration of the mitochondria associated with specific degrees of contracture. In addition to its prior applications, this model seems well suited for investigation of the interdependence of high-energy phosphate levels, ischemic contracture, and mitochondrial function as affected by specific protective interventions designed to limit ischemic injury.
Adenosine Triphosphate↗
Measurement of global ventricular function in patients during cardiac operations using sonomicrometry.
In these studies, we evaluated the applicability of pulse-transit sonomicrometry for measuring changes in global cardiac activity in patients during cardiac operative procedures. In six patients two epicardial ultrasonic crystals (8 mm) were sutured across the left ventricular minor axis. Diastolic pressure-length data were recorded as left ventricles were filled passively to transmural pressures (P) from 0 to 20 mm Hg. Data were collected at the beginning of cardiopulmonary bypass and again 15 minutes following periods of induced global ischemia (29.8 +/- 0.8 minutes). Minor axis length data were normalized to Lagrangian strain (epsilon), and best-fit regression curves were obtained from P-epsilon by computer analysis. Nonlinear elastic constants, alpha and beta, were mathematically derived as additional curve descriptors. Decreases in ventricular compliance were demonstrated as leftward shifts in both computed and measured P-epsilon curves. Global ischemia appeared to effect a decrease in overall ventricular diastolic compliance in all patients studied (p =7E 0.01 at 5, 10, 15, 20 mm Hg). Simultaneously, no statistical change occurred in lo (62.93 +/- 2.80 mm), which represented end-diastolic length (EDL) at 0 mm Hg transmural pressure. Following coronary grafting several patients showed augmented systolic excursion when compared at similar EDL. For those analyses, shortening was compared at specific minor axis EDLs rather than filling pressures. These data indicate that experimentally developed sonomicrometry may safely provide accurate indices of systolic and diastolic ventricular properties during operations necessitating cardiopulmonary bypass. Thus various cardioplegic solutions, ischemic arrest periods, and inotropic agents may be evaluated more objectively.
Blood Pressure↗