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Biomedical subjects

H H Young

Publications and source records attributed to H H Young.

At least 37 records · Page 2Linked to original sources
PubMed1993

Cardiopulmonary dysfunction produced by reoxygenation of immature hypoxemic animals supported by cardiopulmonary bypass. Prevention by intravenous metabolic pretreatment.

This study tests the hypothesis that reoxygenation injury is produced when cardiopulmonary bypass is initiated in immature hypoxemic piglets and that it causes cardiopulmonary dysfunction that can be avoided by intravenous metabolic treatment before and during cardiopulmonary bypass. Of 18 immature Yorkshire-Duroc piglets (aged < 3 weeks), six were anesthetized, instrumented, and observed for 5 hours (control animals). Twelve piglets underwent up to 2 hours of hypoxemia (arterial oxygen tension = 20 to 30 mm Hg) before initiation of reoxygenation on cardiopulmonary bypass. Six received an intravenous metabolic infusion solution (mercaptopropionyl glycine, catalase, aspartate, glutamate, glucose/insulin), which was started before and continued during cardiopulmonary bypass. Hypoxia produced an initial hyperdynamic response (39% increase in cardiac index; p < 0.05) followed by progressive hemodynamic deterioration, necessitating premature initiation of bypass in 8 of 12 hypoxemic piglets (67%). Reoxygenation-induced injury (assessed 30 minutes after cardiopulmonary bypass) was characterized by 39% reduction of stroke work index (p < 0.05), increased myocardial lipid peroxidation (79% increase of conjugated dienes; p < 0.05), 254% increase in pulmonary vascular resistance index (p < 0.05), 22% decrease in static lung compliance (p < 0.05), and 50% decrease in arterial/alveolar oxygen tension ratio (p < 0.05). These reoxygenation changes were avoided by intravenous metabolic treatment. We conclude that the reoxygenation of immature hypoxemic piglets by initiating cardiopulmonary bypass results in cardiopulmonary dysfunction that may increase vulnerability to subsequent ischemia (i.e., aortic crossclamping). The cardiopulmonary reoxygenation changes are preventable by intravenous metabolic treatment before and during cardiopulmonary bypass needed for cardiac repair.

Animals↗
PubMed1992

Role of L-arginine-nitric oxide pathway in myocardial reoxygenation injury.

In view of the recent findings that NO reacts with superoxide anion to generate hydroxyl radical, the present study was conducted to ascertain the role of endogenous NO in mediating myocardial reoxygenation injury in the hypoxic piglet on cardiopulmonary bypass. Anesthetized piglets were made hypoxic (PaO2 = 20-30 mmHg) for up to 120 min, followed by reoxygenation on cardiopulmonary bypass for 30 min. Reoxygenation caused rapidly developing myocardial injury characterized by decreased contractility (expressed as end-systolic elastance) and increased lipid peroxidation (measured as conjugated dienes). Systemic venous and coronary sinus blood content of NO decreased significantly during hypoxia and increased substantially above prehypoxic levels during reoxygenation on cardiopulmonary bypass. Administration of either the antioxidants mercaptopropionyl glycine and catalase or the NO synthase inhibitor, NG-nitro-L-arginine methyl ester, to the extracorporeal circuit afforded similar and nearly complete protection against myocardial reoxygenation injury. The protective effects of NG-nitro-L-arginine methyl ester were nullified by adding an excess of L-arginine to the pump circuit, suggesting that the L-arginine-NO pathway is involved in myocardial reoxygenation injury.

Animals↗
PubMed1991

Donor hearts with impaired hemodynamics. Benefit of warm substrate-enriched blood cardioplegic solution for induction of cardioplegia during cardiac harvesting.

Brain-dead donors frequently show circulatory deterioration and often require so much inotropic support that the donor heart is of questionable value. This experimental study quantifies the cardiac metabolic consequences of brain death and the role of warm blood cardioplegic solution for induction of cardioplegia to improve the quality of potential donor hearts with impaired hemodynamics. Twelve dogs were subjected to brain death by interrupting cerebral blood flow (ligation of innominate artery, carotid arteries, and superior vena cava) and were followed up for as long as 6 hours. Each showed progressive hemodynamic deterioration, necessitating inotropic support (dopamine, calcium, and epinephrine) and large amounts of volume replacement (hetastarch; Hespan) to support the circulation (maintain mean arterial blood pressure greater than 60 mm Hg). Biopsy specimens were taken after 6 hours, or when irreversible ventricular fibrillation occurred, and were analyzed for adenosine triphosphate, creatine phosphate, glycogen, glutamate, and lactate. In six dogs the aorta was then clamped, and a 10-minute infusion of warm (37 degrees C) substrate-enriched aspartate/glutamate blood cardioplegic solution (with the dog's own blood) was given by roller pump to simulate warm induction during the harvesting process. Biopsies were then repeated. Myocardial metabolism, expressed as percent of control values, during brain death was characterized by the following: (1) moderate energy depletion (adenosine triphosphate fell 25% +/- 8%, creatine phosphate fell 55% +/- 15%; p less than 0.05 versus control: mean +/- standard error of the mean); (2) substrate depletion (tissue glutamate fell 48% +/- 9.5%, glycogen fell 66% +/- 7.5%; p less than 0.05 versus control: mean +/- standard error of the mean); and (3) evidence of anaerobic metabolism (lactate increased 374% +/- 95%; p less than 0.05 versus control: mean +/- standard error of the mean). Warm induction of blood cardioplegia in these energy- and substrate-depleted ischemic hearts showed (1) return of creatine phosphate levels to normal (113% +/- 16.8%), (2) replenishment of glutamate (201% +/- 24% of control; p less than 0.05 versus control: mean +/- standard error of the mean), and (3) 43% +/- 14% reduction in myocardial lactate content; (p less than 0.05 versus brain-dead animals). These data suggest that brain-dead donors requiring inotropic support sustain energy and substrate depletion and ischemic damage that can be reversed by a brief period of induction of cardioplegia with a warm substrate-enriched blood cardioplegic solution before harvesting.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Studies of myocardial protection in the immature heart. III. Models of ischemic and hypoxic/ischemic injury in the immature puppy heart.

This study compares the metabolic and functional effects of three different models of ischemia in the immature heart. The intent was (1) to develop a model of energy-depleted and functionally depressed heart to be used in subsequent studies of myocardial protection and (2) to characterize the biochemical changes following different interventions. Forty-five minutes of normothermic global ischemia produced severe depletion of adenosine triphosphate and creatine phosphate (greater than 70%) but was associated with 85% +/- 10% recovery of left ventricular function. Postischemic functional depression (less than 30% recovery) could be produced by either (1) extending the ischemic duration to 60 minutes or (2) preceding 45 minutes of ischemia by 60 minutes of hypoxic stress (oxygen tension 25 to 30 mm Hg). Neither of these more severe interventions caused more profound depletion of adenosine triphosphate or creatine phosphate, but hypoxic stress produced marked tissue depletion of glutamate (52%) and aspartate (48%) before aortic clamping. Longer ischemia or preceding hypoxia led to greater myocardial accumulation of lactate (greater than 250 versus 104 mumol/gm dry weight) and succinate (18 versus 11 mumol/gm dry weight) during aortic clamping, p less than 0.05 versus 45 minutes of ischemia) and greater postischemic depression and amino acid (greater than 65% aspartate depletion) and carbohydrate (greater than 50% glycogen depletion) metabolism, p less than 0.05 versus simple ischemia. These findings suggest that more severe ischemic/hypoxic models are needed in immature hearts to produce functional depression, and the biochemical analyses suggest the characteristics of metabolic defects that must be corrected to resuscitate these hearts during surgical correction of congenital defects.

Adenosine Triphosphate↗
PubMed1991

Studies of myocardial protection in the immature heart. IV. Improved tolerance of immature myocardium to hypoxia and ischemia by intravenous metabolic support.

Thirteen immature puppies (2 to 4 kg) underwent 1 hour of acute hypoxia (oxygen tension 25 to 30 mm Hg), followed by 45 minutes of normothermic global ischemia on total vented bypass with normal blood reperfusion. Ventricular function was assessed by inscribing Starling function curves and measuring stroke work indices before hypoxia and after reperfusion. Seven puppies (control) received normal saline infusion at 4 ml/kg/hr. Six other puppies received a 4 ml/kg/hr intravenous infusion of glutamate/aspartate, glucose-insulin-potassium, mercaptopropionyl glycine, carnitine, and catalase during hypoxia and reperfusion. In control hearts, acute hypoxia depleted myocardial glutamate and aspartate by 52% (p less than 0.05 versus prehypoxia) and 48% (p less than 0.05 versus prehypoxia) and caused severe hemodynamic deterioration (55% decrease of stroke work index) (p less than 0.05 versus prehypoxia); three of seven (43%) required premature institution of bypass. Postischemic left ventricular function recovered to only 40% of control levels (p less than 0.05 versus prehypoxia). In contrast, intravenous metabolic infusions maintained tissue glutamate (p less than 0.05 versus control group) and aspartate (p less than 0.05 versus control group) in treated hearts during hypoxia and allowed cardiac index to rise 20% (p less than 0.05 versus prehypoxia); all treated hearts tolerated 1 hour of hypoxia, and stroke work recovered 70% (p less than 0.05 versus control group) of stroke work index after subsequent ischemia. Impaired tolerance of immature hearts to acute hypoxia and subsequent ischemia is due to substrate depletion. This impairment can be reduced by intravenous metabolic support during hypoxia and reperfusion and leads to improved recovery of postischemic function.

Animals↗
PubMed1990

Preliminary results in invasive bladder cancer with transurethral resection, neoadjuvant chemotherapy and combined pelvic irradiation plus cisplatin chemotherapy.

Preliminary data are presented of a clinically feasible pilot study to select a significant subgroup of patients among those with muscle-invading bladder tumors for local cure and bladder preservation, while also to offer all patients the possibility of preventing the development of distant metastases. Transurethral debulking surgical resection was combined with neoadjuvant methotrexate, cisplatin and vinblastine chemotherapy plus 2 additional courses of cisplatin and 4,000 cGy. If tumor was found on cystoscopic re-evaluation by biopsy and for cytology after cisplatin and partial irradiation (4,000 cGy.) immediate cystectomy was advised. If tumor was not found consolidation by a radiotherapy boost to a total of 6,480 cGy. plus 1 additional course of cisplatin was given. Of 53 consecutive patients the planned treatment was completed in 42 (79%). With a median followup of 26 months (range 15 to 42 months), 72% of all entered patients were alive, 70% have not required cystectomy and 74% have not had distant metastases. Among the 42 patients who completed the planned protocol chemotherapy dose reductions were required in 39% for stomatitis, bone marrow depression and/or renal dysfunction. There were 2 serious complications but no treatment-related sepsis, deaths or significant renal dysfunction. Eight patients underwent immediate radical cystectomy because of positive biopsy and/or cytology results after 4,000 cGy., while 34 completed full chemotherapy and radiotherapy without any significant bladder or bowel injury. Of 42 patients 22 (52%) have maintained the bladder without any recurrence, and of those selected for full chemotherapy and radiotherapy this number increased to 65%. To date 12 patients have persistent or recurrent bladder tumors: 5 (15%) had invasive tumors treated by cystectomy and 7 (21%) had carcinoma in situ treated by intravesical therapy. The true success of this or other selective bladder-preserving treatments will require 3 to 5 years of followup to be confident that such treatment has sterilized the bladder of cancer. This feasibility study has been clinically practical, modestly well tolerated and encouraging for the significant proportion of patients with a sustained complete response and for the 70% over-all survival rate at 2 years. To evaluate critically the efficacy of methotrexate, cisplatin and vinblastine chemotherapy in the prevention of occult distant micrometastases and in increasing the rate of successful bladder preservation, in May 1988 we began a randomized phase 3 trial with and without neoadjuvant methotrexate, cisplatin and vinblastine chemotherapy.

Aged↗
PubMed1990

Studies of myocardial protection in the immature heart. I. Enhanced tolerance of immature versus adult myocardium to global ischemia with reference to metabolic differences.

This study compares the metabolism and functional responses of adult and immature hearts to a standard ischemic insult. Ten adult dogs (25 to 27 kg) and 10 puppies (6 to 10 weeks old) underwent 45 minutes of aortic clamping on bypass. Preoperative and postoperative ventricular performance (Starling curves), biochemical factors, and water content were measured. Global ischemia in adults produced a 30% mortality rate (3/10) and low output syndrome in survivors (33% recovery of stroke work index). Conversely, all puppies survived and stroke work index returned to 85% of control, with less edema developing (0.4% versus 2% water gain, p less than 0.05). Puppies expended comparable glycogen stores but used more glutamate (15.4 versus 8.6 mumol/gm dry weight), produced more alanine (18.9 versus 6.4 mumol, p less than 0.05), succinate (19 versus 8.2 mumol, p less than 0.05), and malate (2.6 versus 0.15 mumol, p less than 0.05) during ischemia, and recovered better postischemic aerobic metabolism (410 versus 255 nmol tissue pyruvate, p less than 0.05). We conclude that tolerance of immature hearts to ischemia is related to amino acid utilization by transamination and increased substrate level phosphorylation, as occurring in diving mammals, suggesting retention of intrautero adaptive mechanisms.

Adenosine Triphosphate↗
PubMed1990

Studies of myocardial protection in the immature heart. II. Evidence for importance of amino acid metabolism in tolerance to ischemia.

This study tests the importance of amino acid transamination in determining the tolerance of immature hearts to ischemic damage. Amino acid transamination was inhibited metabolically by pretreatment with aminooxyacetic acid. The aminooxyacetic acid dose and duration were determined by incubating in vitro tissue homogenate and showing that an 8 mmol/L AOA dose for 5 minutes blocked 90% of alanine aminotransferase and aspartate aminotransferase activity. Control studies in nonischemic hearts showed that coronary perfusion with aminooxyacetic acid for 5 minutes did not impair myocardial performance. In contrast, pretreatment of immature puppies with aminooxyacetic acid severely impaired recovery after 45 minutes of normothermic global ischemia (30% versus 85% recovery in untreated hearts, p less than 0.05). Biochemical analyses of hearts undergoing ischemia showed aminooxyacetic acid to limit lactate production, impair glutamate utilization, prevent alanine production, and limit succinate accumulation (p less than 0.05). These data suggest that amino acid transamination is an important adaptive process in the immature heart that improves its resistance to ischemic damage.

Adenosine Triphosphate↗
PubMed1989

Studies on prolonged acute regional ischemia. V. Metabolic support of remote myocardium during left ventricular power failure.

This study tests the hypothesis that metabolic support of remote "nonischemic" myocardium during acute infarction will reverse the trend toward cardiogenic shock. Thirty-seven dogs underwent ligation of the left anterior descending coronary artery and 50% stenosis of the circumflex coronary artery. Irreversible ventricular fibrillation developed in 11 of them. The 26 survivors were observed for up to 6 hours; global and regional left ventricular function (cardiac index, stroke work index, ultrasonic crystals) and regional blood flow (radioactive microspheres) were measured. After 2 hours, eight dogs received an intravenous infusion of glutamate/aspartate, glucose-insulin-potassium, coenzyme Q10, and 2-mercapto-propionyl-glycine for 4 hours. Five dogs received the mannitol infusion to raise serum osmolarity 30 mOsm. Four additional dogs received the intravenous substrate infusions over 4 hours without undergoing ischemia. The substrate infusion for 4 hours caused no change in regional or global cardiac function in the four control dogs. Three of nine untreated dogs died of cardiogenic shock, and progressive left ventricular power failure occurred in the six others (40% decrease in cardiac index, 50% decrease in stroke work index, p less than 0.05) because of persistent dyskinesia in the left anterior descending region (-40% of systolic shortening, p less than 0.05) and hypocontractility in the circumflex region (48% of control systolic shortening, p less than 0.05), despite normal transmural blood flow in the posterior left ventricular wall (76 ml/100 gm/min). In contrast, in treated dogs, hypercontractility recovered in the circumflex segment (138% of systolic shortening) and stroke work index rose to control levels (91%) without a change in regional blood flow. Mannitol infusion did not improve hemodynamics or avoid the development of progressive left ventricular power failure. We conclude that cardiogenic shock after myocardial infarction is due, in large part, to impaired ability of "nonischemic" myocardium to maintain hypercontractility. This limitation can be prevented by metabolic support of viable muscle, and the data imply that intravenous substrate infusions may be helpful before definitive treatment (i.e., coronary artery bypass grafting) is undertaken.

Animals↗
PubMed1989

Studies on prolonged acute regional ischemia. I. Evidence for preserved cellular viability after 6 hours of coronary occlusion.

Six hours of coronary occlusion has been thought to produce extensive and irreversible transmural damage and no possibility of salvage by reperfusion. This has been based on findings of adenosine triphosphate depletion and histochemical (triphenyltetrazolium chloride nonstaining) and ultrastructural changes (conventional preparatory techniques). This study tests the hypothesis that, in contrast to conventional wisdom, considerable structural and mitochondrial functional integrity remains in cardiac muscle subjected to 6 hours of regional ischemia. Twenty open-chest anesthetized dogs underwent isolation of the left anterior descending coronary artery and were observed for 6 hours. Eight of the 20 did not undergo ischemia and served as controls. Twelve underwent 6 hours of proximal ligation of the left anterior descending coronary artery (30% +/- 2% area at risk). Transmural biopsy specimens were analyzed. Coronary occlusion reduced regional blood flow (radioactive microspheres) to less than 10 ml/100 gm/min (p less than 0.05) and dyskinesia persisted in the area at risk for 6 hours. High-energy phosphates (adenosine triphosphate and creatine phosphate) declined to negligible levels and histochemical damage occurred (49% +/- 12% triphenyltetrazolium chloride non-staining). Mitochondrial ultrastructural changes (low protein denaturation embedding technique) were mild (the integrity of the inner and outer mitochondrial surface membranes and crystal membranes was maintained and myofibrillar degeneration did not occur). Mitochondrial oxidative phosphorylation rate remained at 63% of control levels, respiratory control index remained at 77%, and adenosine diphosphate/oxygen ratio was maintained at 96%. Mitochondrial Ca++ increased with lanthanum (from 26 to 46 nmol/mg protein, p less than 0.05), but irreversible calcium precipitation did not occur; calcium could be mobilized to normal levels (i.e., 13 nmol/mg protein) by ethylenediaminetetraacetic acid chelation. These data support our inference that necrosis does not occur after 6 hours of coronary occlusion and suggest that muscle salvage by reperfusion is possible after at least 6 hours of regional myocardial ischemia.

Adenosine Triphosphate↗
PubMed1989

Studies on prolonged acute regional ischemia. II. Implications of progression from dyskinesia to akinesia in the ischemic segment.

This study analyzed the pattern of regional wall motion in 58 dogs undergoing 4 to 6 hours of left anterior descending coronary artery occlusion. Regional wall motion was measured by ultrasonic crystals and ischemic muscle either remained dyskinetic (-40% of control systolic shortening, n = 26) or progressed toward akinesia (less than 20% of control systolic shortening or greater than 50% reduction in passive lengthening, n = 32). Ten dogs underwent unmodified blood reperfusion. Regional blood flow (radioactive microspheres), histochemical damage (triphenyltetrazolium chloride staining), and mitochondrial function were determined. Hearts showing persistent dyskinesia had more collateral flow (12 versus 2 ml/100 gm/min, p less than 0.05), less histochemical damage (26% versus 63% area at risk/area of nonstaining, p less than 0.05), and better retention of mitochondrial oxidative phosphorylation capacity (adenosine triphosphate, 622 versus 444 nmol/mg protein/min, p less than 0.05), and tended toward mitochondrial calcium accumulation (48 versus 64 nmol/mg protein). Unmodified blood reperfusion after 4 hours of ischemia produced prompt akinesia (-2% +/- 3% systolic shortening) and was associated with increased edema (82% water content), caused the low-reflow phenomenon (19% control subendocardial flow, 13 ml/100 gm/min), and increased histochemical damage (69% triphenyltetrazolium chloride nonstaining, p less than 0.05). These findings suggest that persistent dyskinesia during early ischemia (first 6 hours) may reflect a relatively optimistic sign, as regression to akinesia occurs in muscle with less collateral flow, more impaired mitochondrial function, worsened calcium homeostasis, and more severe histochemical and ultrastructural damage. These observations imply that careful evaluation of ischemic wall motion may provide a valuable insight into potential muscle salvage.

Adenosine Triphosphate↗
PubMed1989

Studies on prolonged acute regional ischemia. III. Early natural history of simulated single and multivessel disease with emphasis on remote myocardium.

The early natural history of left anterior descending coronary artery occlusion was studied in 35 open-chest anesthetized dogs observed for 6 hours. Six control dogs underwent isolation of the left anterior descending without occlusion, 13 underwent isolated occlusion of the artery to simulate single-vessel disease, and 14 underwent occlusion of the left anterior descending and 50% stenosis of the circumflex coronary artery to simulate multivessel disease. Regional systolic shortening was measured by ultrasonic crystals. Control dogs had a mild fall in cardiac output (27%) and rise in aortic pressure (15 mm Hg). Ischemia produced immediate dyskinesia (-60% of control systolic shortening), and passive lengthening persisted for 6 hours. All dogs with only occlusion of the left anterior descending artery survived (0% mortality). They were less prone to ventricular fibrillation (46% versus 79%, p less than 0.05), developed compensatory hypercontractility of remote muscle (131% of control systolic shortening, p less than 0.05), mild energy and substrate depletion, and anaerobic metabolism (increased glucose-6-phosphate, p less than 0.05) despite maintenance of "normal" blood flow. In contrast, the early mortality rate was 57% (p less than 0.05) when 50% circumflex stenosis coexisted. Intractable ventricular fibrillation and/or cardiogenic shock caused the deaths. Remote muscle became progressively hypocontractile (61% of control systolic shortening, p less than 0.05), with progressive reduction in stroke work index (less than 0.5 gm-m/kg, p less than 0.05). Remote muscle showed moderate substrate and energy depletion (greater than 60% fall of adenosine triphosphate and creatine phosphate, 37% fall of glutamate) and more pronounced evidence of anaerobic metabolism (glucose-6-phosphate rose greater than 400%, p less than 0.05) despite normal blood flow. Mitochondrial ultrastructure and function remained intact in all hearts. These findings suggest that remote muscle is the principal determinant of mortality after an otherwise nonlethal ischemic event. Functional deterioration despite normal blood flow to remote muscle suggests either autoregulatory failure or substrate depletion as a cause of hypocontractility. The structural and functional integrity of mitochondria in ischemic and remote myocardium implies that salvage is possible despite hemodynamic deterioration and intractable ventricular fibrillation.

Adenosine Triphosphate↗
PubMed1989

Studies on prolonged acute regional ischemia. IV. Aggressive surgical treatment for intractable ventricular fibrillation after acute myocardial infarction.

Of 21 dogs undergoing ligation of the left anterior descending coronary artery and 50% stenosis of the left circumflex coronary artery, 15 developed intractable ventricular fibrillation and underwent 1 added hour of femoro-femoral bypass. Three hearts were removed after 1 hour on bypass without myocardial reperfusion for biochemical and mitochondrial analysis. After the 1 hour, five underwent unmodified blood reperfusion on bypass; seven underwent 1 hour of aortic clamping on vented bypass to simulate coronary artery bypass grafting with multidose blood cardioplegic reperfusion. Regional systolic shortening was measured with ultrasonic crystals and cardiac output was measured by thermodilution techniques. All six hearts with no ventricular fibrillation or with reversible ventricular fibrillation and hearts that were not reperfused developed cardiogenic shock (40% decrease in stroke work index, p less than 0.05) because of persistent left ventricular dyskinesia (-40% of systolic shortening, p less than 0.05) and progressive circumflex hypocontractility (48% systolic shortening, p less than 0.05) and showed extensive (68%) triphenyltetrazolium chloride nonstaining. Two dogs died of left ventricular power failure (33% mortality rate). In contrast, 11 of 12 dogs that were reperfused could be weaned from bypass (8% mortality rate). The four dogs surviving after unmodified blood reperfusion (20% mortality rate) showed severe residual left ventricular dysfunction (39% of control stroke work index, p less than 0.05), had equivocal recovery of anterior contractility (10% +/- 7% of systolic shortening), had marginal recovery of contractility in the remote myocardium (60% +/- 11% of systolic shortening), and had extensive triphenyltetrazolium chloride nonstaining (58%). Conversely, all seven dogs with intractable ventricular fibrillation undergoing controlled reperfusion after 4 hours of ischemia recovered normal stroke work index (91%), regained 23% of systolic shortening in the region supplied by the left anterior descending coronary artery (p less than 0.05), 125% of systolic shortening in the circumflex region (p less than 0.05), and showed only 25% triphenyltetrazolium chloride nonstaining (p less than 0.05). These results suggest aggressive treatment of intractable ventricular fibrillation after acute myocardial infarction by providing reperfusion on bypass can salvage hearts thought previously to be damaged irreversibly.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Radiation therapy for localized prostate carcinoma: experience at the Massachusetts General Hospital (1973-1981).

The success following irradiation in 370 patients with clinically localized prostate carcinoma was measured by overall patient survival as well as the cumulative incidence with time of treated patients who developed either local tumor regrowth or progression with distant metastases. With a minimum follow-up of 5 years in living patients, we evaluated the cumulative frequency curves using both univariate and multivariate (Cox) analyses. Overall patient survival and probability of progression with distant metastases were significantly influenced by initial tumor stage and the degree of histologic differentiation. The results at 8 years are significantly better for patients with T2 (B) tumors (local regrowth in 8%, distant metastases in 18%) than for patients with T3-T4 (C) tumors (local regrowth in 28%, distant metastases in 60%). Patient tolerance of external-beam radiation therapy was carefully analyzed in 121 consecutively treated patients in 1980 and 1981 for subsequent radiation-related sequelae. Minor transient intestinal and urologic sequelae were observed in 21% and 23% of the patients, respectively. These mild to moderate symptoms resolved in all but 7% of the patients who are continuing with mild symptoms. One patient had a major complication, i.e., a cystectomy required for persistent bleeding. Erectile potency has been maintained in 63% of potent patients. No specific benefit or detriment in outcome was seen in the minority of 51 patients who were irradiated by iodine-125 implantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1986

Percutaneous ultrasonic lithotripsy of symptomatic renal calculi in children.

Percutaneous ultrasonic lithotripsy of upper urinary tract lithiasis is a well-established procedure in adults. We successfully applied this technique to completely remove symptomatic renal calculi in two children with idiopathic hypercalciuria. The procedure was well tolerated and no complications occurred. Both patients were discharged within 4 days of the lithotripsy. This method is an alternative to surgery for the removal of large or impacted calculi from the upper urinary tracts of pediatric patients.

Adolescent↗
PubMed1986

The effect of glutamate on hypoxic newborn rabbit heart.

Effects of glutamate on myocardial mechanical function and energy metabolism during 120 min of hypoxia and subsequent reoxygenation were studied in the isolated arterially perfused newborn and adult rabbit hearts. The muscle was perfused with a Krebs-Henseleit (KH) solution or KH solution which contained 1 mM glutamate. Glutamate attenuated the effects of hypoxia on mechanical function and tissue ATP concentration, and enhanced the recovery of mechanical function and tissue ATP during reoxygenation. During hypoxia, glutamate increased tissue succinate and GTP with no change in total lactate and pyruvate production. Trace studies using 14C-glutamate and the tissue homogenate showed that hypoxia increased tissue succinate and inhibited TCA cycle. Additional glutamate produced more CO2 and TCA intermediates in both oxygenated and hypoxic mediums. These data indicate that glutamate increased the rate of ATP production in the hypoxic and reoxygenated heart. This study shows that the improvement of mechanical function and ATP formation in the hypoxic myocardium by glutamate was due to an increase in both oxidative phosphorylation and substrate level phosphorylation. The effect of glutamate on the ATP and GTP production in the newborn heart was not different from the adult.

Adenosine Triphosphate↗
PubMed1986

Ureteroscopy: the initial experience.

A prospective study of our first 81 cases of ureteroscopy using extended length rigid endoscopes was performed. Of 55 stone manipulations attempted in 51 patients by 6 endoscopists 38 (69 per cent) were successful. Analyzed sequentially, removal was successful in 12 of 23 attempts (52 per cent) among the initial 40 patients and in 26 of 32 (81 per cent) among the subsequent 41 patients. Of 11 calculi larger than 1 cm. and of 23 positioned above the iliac vessels 7 (64 per cent) and 11 (48 per cent), respectively, were removed successfully. Disimpaction by ureteroscopic manipulation combined with extracorporeal shock wave lithotripsy was successful in 4 cases of upper ureteral calculi not treatable by extracorporeal shock wave lithotripsy alone. Diagnostic and therapeutic uses of the ureteroscope in addition to treatment of ureteral calculi have included the delineation of ureteral filling defects (9 patients), fulguration of known low grade tumors (4) and dilation of ureteral strictures (5). In 10 patients information was obtained endoscopically that was not possible by standard diagnostic techniques. The direct visual approach to the ureter has distinct advantages over blind ureteral instrumentation.

Adult↗