[Clinical characteristics of patients with indication of cardiac implantable electronic devices implantation complicating with acute pulmonary thromboembolism].

Objective: To investigate the clinical characteristics of inpatients with the indication of cardiac implantable electronic devices (CIED) therapy and combined acute pulmonary thromboembolism (APTE). Methods: We retrospectively screened 8 641 inpatients who admitted with the indication of CIED implantation in Fuwai Hospital from January 2014 to May 2019. The clinical characteristics, management strategies and clinical outcome were analyzed for patients diagnosed as APTE. Results: APTE were identified in 45 (5‰) patients in this cohort, there were 18(40%) male patients, the average age was (73±8) years old and body mass index was (27±10) kg/m2.Thirty-two (70%) patients were at intermediate-risk and 13 (30%) at low-risk. Anti-coagulation therapy was initiated in 38(84%) patients, and 30 patients underwent CIED implantation (27 pacemaker, 2 CRT and 1 ICD). No postoperative bleeding or pocket hematoma were detected in the 23 patients taking anticoagulation medication before implantation. During an average of (30±7) months' follow up, thrombus was dissolved in 20 patients, hemorrhage complications were observed in 2 patients (1 cerebral hemorrhage and 1 hematuria), anticoagulation therapy was discontinued in these 2 patients. Among 15 patients without immediate CIED implantation and treated with anticoagulation therapy during hospitalization, 2 patients developed complete paroxysmal Ⅲ° atrioventricular block, and recovered after therapy during hospitalization. Seven patients were re-hospitalized for CIED implantation due to bradycardia. Five patients died during follow-up (3 sudden cardiac death, 1 APTE combined with cerebral infarction, and 1 pulmonary infection). Conclusion: APTE is not rare in patients with the indication of CIED implantation, CIED implantation and anti-coagulation therapy are safe for these patients, and transient atrioventricular block could be detected in APTE patients.

[Clinical value of fluorescence in situ hybridization positive of exfoliated urothelial cells in urothelial carcinoma].

OBJECTIVE: To analyze the clinical pathologic characteristics of cases with fluorescence in situ hybridization (FISH) positive of exfoliated urothelial cells, so as to evaluate the clinical utility of FISH in the diagnosis of urothelial carcinoma (UC). METHODS: A total of 271 cases of FISH positive in Department of Urology of Peking University First Hospital from Apr. 2012 to Sep. 2015 were recruited in this study. Retrospective analysis was made on their clinical data. For FISH analysis, labeled probes specific for chromosomes 3, 7, 17, and the p16 (9p21) gene were used to assess chromosomal abnormalities indicative of malignancy. The positive predict values (PPV) of all the techniques were analyzed. RESULTS: Of the 271 patients, 207 cases were UC, 7 cases were non-UC, and 57 cases were benign diseases. The PPV of FISH in detecting UC was 76.4%, while the 95% confidence interval (CI) 71.3% to 81.5%. In the cohort of FISH positive, this value was similar to that of urinary cytology (PPV 86.8%, 95% CI: 78.5%-95.0%). The PPV of FISH was lower than that of cystoscopy and ureteroscopy (PPV 96.1%, 95% CI: 91.7%-100.0%). There were significant differences between this study and the PPV of FISH reported abroad (PPV 53.9%, χ2=33.048, P<0.001). Of all the UC with FISH positive, bladder cancer showed an earlier pathological stage versus renal pelvic carcinoma and ureteral carcinoma, with significance (χ2=5.894, P=0.015, and χ2=13.601, P<0.001, respectively). However, no difference was found in the size, pathological stage and pathological grade of tumors between the urinary cytology positive group and the urinary cytology negative group. The rate of high-grade UC in ureteral carcinoma of FISH positive was 92.3%, much higher than that of ureteral carcinoma reported domestically. CONCLUSION: The PPV of FISH in detecting UC is higher relatively, with a better clinic value for Chinese patients. The ureteral carcinoma with FISH positive obtains a higher pathological grade, which is of great guiding significance for UC.

[Concurrent renal cell carcinoma and urothelial carcinoma: long-term follow-up study of 24 cases].

Objective: To investigate the clinical manifestation, diagnosis, treatment and outcome of simultaneous occurrence of renal cell carcinoma and urothelial carcinoma. Methods: Twenty-four consecutive patients with synchronous renal cell carcinoma and urothelial carcinoma treated in our center from March 2005 to December 2015 were retrospectively reviewed. Their clinical, pathological and prognostic features were evaluated. Kaplan-Meier curves were used to estimate overall survival. Results: Patient' age was range from 48 to 79 yrs (median 69.5). Fourteen patients presented with macroscopic hematuria, and 10 patients were asymptomatic. B-ultrasound, computed tomography (CT) and cystoscopy initially indicated renal cell carcinoma concurrent with ipsilateral upper urinary tract urothelial carcinoma (UTUC) in 4 cases, renal cell carcinoma concurrent with bladder tumor in 16 cases, renal cell carcinoma concurrent with both ipsilateral UTUC and bladder tumor in 1 case, renal cell carcinoma in 2 cases and ureter carcinoma in 1 case. Different treatments were performed. The median follow-up time after surgery was 22.5 months. For patients with synchronous renal cell carcinoma and bladder tumor, there was no significant survival difference between patients treated with partial nephrectomy or radical nephrectomy. During follow up, 3 patients died of renal cell carcinoma, 3 patients died of non-oncological disease and 1 patient died of ureter carcinoma. The 3-year overall survival rate was 82.7%. For patients with synchronous renal cell carcinoma and bladder tumor, there was no significant survival difference between patients treated with partial nephrectomy or radical nephrectomy (P=0.874). Conclusions: Concurrence of renal cell carcinoma and urothelial carcinoma is clinically rare. Treatments should be individualized. The prognosis for a patient with synchronous renal cell carcinoma and urothelial carcinoma is associated with the more aggressive one.

[Clinical significance of residual tumors at repeat transurethral resection in patients with T1 bladder cancer].

OBJECTIVE: To investigate the predictors of residual tumors at repeat transurethral resection of bladder tumors (re-TURBT) for the patients with T1 bladder cancer and evaluate the effect of the residual tumors on the prognosis of the disease. METHODS: We reviewed the clinical data of the patients with T1 bladder cancer who underwent re-TURBT from 2008 to 2015 in our department. Seventy-two patients received re-TURBT 2-6 weeks after the initial TURBT. A total of 65 patients were followed up, and we recorded the events of tumor recurrence, tumor progression, radical cystectomy and cancer specific death.The influencing factors of re-TURBT positive rate were analyzed.The effects of re-TURBT positive or negative findings on the prognosiswere compared. RESULTS: 33.3% of the patients who received re-TURBT had residual tumours. Re-TURBT positive in T1 bladder cancer has significant correlation with tumor size (P<0.05). Residual tumors tended to be detected in patients with larger tumors (diameter ≥ 4 cm) but might have no relationship with tumor grade or tumor number. The recurrence rate within 3 month ofthe patients with residual tumours at re-TURBT was 25% (5/20), while there were no patients suffering recurrence who had no residual tumours at re-TURBT, which had a significant difference (P<0.001). However, the overall recurrence rate, progression rate, rate of radical cystectomy and cancer specific mortality showed no significant difference between the two groups (45% vs 40%, P=0.71; 10% vs 6.7%, P=0.64; 5% vs 8.9%, P=0.59; 5% vs 2.2%, P=0.55). CONCLUSIONS: For the patients with T1 bladder cancer, larger tumors could be a predictor for residual tumors at re-TURBT. The presence of residual tumors is associated with early recurrence.

[Effects of NOX4 on radiosensitivity of nasopharyngeal carcinoma cells by activating the PI3K/AKT pathway].

Objective: To explore the relationship between NOX4 and radiosensitivity of nasopharyngeal carcinoma cells. Methods: Western blot was used to test the expression of NOX4 in nasopharyngeal carcinoma cells (CNE1, CNE2 and HONE1) and normal nasopharyngeal epithelial cells (NP69). The lentiviral vectors for RNA interference and overexpression of NOX4 gene were constructed and nasopharyngeal carcinoma cells were transfected. After treatment with radiation or/and PI3K/AKT inhibitor LY294002, the expressions of related proteins in cells were tested by Western blot, and the cell proliferation was detected by CCK-8 assay and the cell apoptosis was determined by flow cytometry. GraphPad Prism 5 was used for statistical analysis, and P<0.05 was statistically significant. Results: The expressions of NOX4 in nasopharyngeal carcinoma cells were higher than those in normal nasopharyngeal epithelial cells. Compared with the siNC group, the siNOX4 group of nasopharyngeal carcinoma cell had lower proliferation capacity [72 h absorbance (A) value:1.16 vs. 0.75] and higher apoptosis rate (2.9% vs. 10.0%). In contrast,compared with the vector group, the NOX4 group of nasopharyngeal carcinoma cell had higher proliferation capacity [72 h absorbance (A) value: 1.01 vs. 1.32] and lower apoptotic rate (1.7% vs. 1.1%).Treatment with LY294002 for nasopharyngeal carcinoma cells of NOX4 overexpression,compared with the NOX4 group, the proliferation ability of nasopharyngeal carcinoma cells in the NOX4+LY294002 group was reduced (72 h absorbance (A) value: 1.32 vs. 0.77), while the apoptotic rate was increased (1.1% vs. 3.1%).Treatment with radiotherapy, compared with the siNC/Vector group, the proliferation ability of nasopharyngeal carcinoma cells in the siNOX4 group was reduced (72 h absorbance (A) value: 0.72 vs. 0.33), and the apoptotic rate was increased (7.8% vs. 17.3%). However, in the NOX4 group, the proliferation of nasopharyngeal carcinoma cells was enhanced (72 h absorbance (A) value:0.65 vs. 0.78), and the apoptotic rate was reduced (8.1% vs. 3.8%). Compared with the NOX4+radiation group, the proliferation ability of nasopharyngeal carcinoma cells in the NOX4+radiation+LY294002 group was reduced (72 h absorbance (A) value: 0.79 vs. 0.56), while the apoptotic rate was increased (3.8% vs. 8.1%). Conclusion: NOX4 can inhibit radiosensitivity of nasopharyngeal carcinoma cells possibly by activating PI3K/AKT pathway.

AKT-GSK3ß Signaling Pathway Regulates Mitochondrial Dysfunction-Associated OPA1 Cleavage Contributing to Osteoblast Apoptosis: Preventative Effects of Hydroxytyrosol.

Oxidative stress (OS) induces osteoblast apoptosis, which plays a crucial role in the initiation and progression of osteoporosis. Although OS is closely associated with mitochondrial dysfunction, detailed mitochondrial mechanisms underlying OS-induced osteoblast apoptosis have not been thoroughly elucidated to date. In the present study, we found that mitochondrial abnormalities largely contributed to OS-induced osteoblast apoptosis, as evidenced by enhanced production of mitochondrial reactive oxygen species; considerable reduction in mitochondrial respiratory chain complex activity, mitochondrial membrane potential, and adenosine triphosphate production; abnormality in mitochondrial morphology; and alteration of mitochondrial dynamics. These mitochondrial abnormalities were primarily mediated by an imbalance in mitochondrial fusion and fission through a protein kinase B- (AKT-) glycogen synthase kinase 3ß- (GSK3ß-) optic atrophy 1- (OPA1-) dependent mechanism. Hydroxytyrosol (3,4-dihydroxyphenylethanol (HT)), an important compound in virgin olive oil, significantly prevented OS-induced osteoblast apoptosis. Specifically, HT inhibited OS-induced mitochondrial dysfunction by decreasing OPA1 cleavage and by increasing AKT and GSK3ß phosphorylation. Together, our results indicate that the AKT-GSK3ß signaling pathway regulates mitochondrial dysfunction-associated OPA1 cleavage, which may contribute to OS-induced osteoblast apoptosis. Moreover, our results suggest that HT could be an effective nutrient for preventing osteoporosis development.

Developmental adaptations in cytosolic phosphate content and pH regulation in the sheep heart in vivo.

This study examines adaptations in myocardial cytosolic phosphate content and buffering capacity that occur in vivo as a function of development. Phosphate metabolites were monitored in an open chest sheep preparation using a 31P magnetic resonance surface coil over the left ventricle. Newborn lambs (aged 4-9 d, n = 5) underwent exchange transfusion with adult blood to reduce blood-borne 2,3-diphosphoglycerate contamination of the heart monophosphate and phosphomonoester resonances, thus allowing determination of these phosphate concentrations. The blood-exchanged newborns and mature controls (aged 30-60 d, n = 5) were infused with 0.4 N hydrochloric acid to decrease pH from greater than 7.35 to less than 7.00. Simultaneously, intracellular and extracellular pH were determined from the chemical shifts of the respective phosphate peaks and compared to arterial blood pH. Findings were as follows: (a) diphosphoglycerate contribution to the cardiac spectrum was found to be negligible, (b) significant decreases in cytosolic phosphate (P less than 0.03) and phosphomonoester (P less than 0.01) content occurred with maturation, and (c) large decreases in extracellular pH (greater than 0.5 U) in both groups were similarly associated with only small changes in intracellular pH (less than 0.1 U). Change in cytosolic phosphate content implies that alterations occur in the phosphorylation potential with resulting effects on regulation of myocardial respiration, and cardiac energetics.

Relation of myocardial oxygen consumption and function to high energy phosphate utilization during graded hypoxia and reoxygenation in sheep in vivo.

This study investigates the relation between myocardial oxygen consumption (MVO2), function, and high energy phosphates during severe hypoxia and reoxygenation in sheep in vivo. Graded hypoxia was performed in open-chested sheep to adjust PO2 to values where rapid depletion of energy stores occurred. Highly time-resolved 31P nuclear magnetic resonance spectroscopy enabled monitoring of myocardial phosphates throughout hypoxia and recovery with simultaneous MVO2 measurement. Sheep undergoing graded hypoxia (n = 5) with an arterial PO2 nadir of 13.4 +/- 0.5 mmHg, demonstrated maintained rates of oxygen consumption with large changes in coronary flow as phosphocreatine (PCr) decreased within 4 min to 40 +/- 7% of baseline. ATP utilization rate increased simultaneously 59 +/- 20%. Recovery was accompanied by marked increases in MVO2 from 2.0 +/- 0.5 to 7.2 +/- 1.9 mumol/g per min, while PCr recovery rate was 4.3 +/- 0.6 mumol/g per min. ATP decreased to 75 +/- 6% of baseline during severe hypoxia and did not recover. Sheep (n = 5) which underwent moderate hypoxia (PO2 maintained 25-35 mmHg for 10 min) did not demonstrate change in PCr or ATP. Functional and work assessment (n = 4) revealed that cardiac power increased during the graded hypoxia and was maintained through early reoxygenation. These studies show that (a) MVO2 does not decrease during oxygen deprivation in vivo despite marked and rapid decreases in high energy phosphates; (b) contractile function during hypoxia in vivo does not decrease during periods of PCr depletion and intracellular phosphate accumulation, and this may be related to marked increases in circulating catecholamines during global hypoxia. The measured creatine rephosphorylation rate is 34 +/- 11% of predicted (P < 0.01) calculated from reoxygenation parameters, which indicates that some mitochondrial respiratory uncoupling also occurs during the rephosphorylation period.

Thyroid hormone coordinates respiratory control maturation and adenine nucleotide translocator expression in heart in vivo.

BACKGROUND: The signal transduction mechanism linking mitochondrial ATP synthesis with cytosolic ATP utilization in heart changes during postnatal development in vivo. This maturational process occurs in parallel with accumulation of mitochondrial adenine nucleotide translocator (ANT), which provides a possible site for respiratory control. We postulated that thyroid hormone regulates these maturational processes. METHODS AND RESULTS: We used (31)P MR spectroscopy to determine the relationship between myocardial high-energy phosphates, phosphocreatine, and ADP and oxygen consumption (MVO(2)) during epinephrine stimulation in 32- to 40-day-old lambs thyroidectomized after birth (THY) and age-matched controls. Steady-state protein and mRNA levels for ANT isoforms and beta-F(1)-ATPase were assessed from left ventricular tissues by Western and Northern blotting. With greater doses of epinephrine, THY attained lower peak MVO(2) than controls (P:<0.05). Controls maintained high-energy phosphate levels, unlike THY, which demonstrated significantly decreased phosphocreatine/ATP and increased cytosolic ADP despite lower peak MVO(2). No significant differences in beta-F(1)-ATPase protein or mRNA occurred between groups. However, ANT isoform mRNA levels were 2-fold greater and protein levels 4-fold greater in control hearts. CONCLUSIONS: These data imply that the maturational shift away from ADP-mediated respiratory control is regulated by thyroid hormone in vivo. Specific thyroid-modulated increases in ANT mRNA and protein imply that this regulation occurs in part at a pretranslational level.

Signaling and expression for mitochondrial membrane proteins during left ventricular remodeling and contractile failure after myocardial infarction.

OBJECTIVES: This study was conducted to test hypotheses stating that: 1) altered signaling for mitochondrial membrane proteins occurs during postinfarction remodeling, and 2) successful myocardial adaptation relates to promotion of specific mitochondrial membrane components. BACKGROUND: Abnormalities in high-energy phosphate content and limitations in adenosine 5'-triphosphate (ATP) synthesis rate occur during the transition to contractile failure from compensatory remodeling after left ventricular infarction. The adenine nucleotide translocator (ANT) and F1-ATPase respectively regulate mitochondrial adenosine 5'-diphosphate (ADP)/ATP exchange and ADP-phosphorylation, which are key components of high-energy phosphate metabolism. METHODS: Steady-state mRNA and protein expression for ANT isoform1 and the beta subunit of the F1-ATPase (betaF1) were analyzed in myocardium remote from the infarction zone eight weeks after left circumflex coronary artery ligation in pigs, demonstrating either successful left ventricular remodeling (LVR, n = 8) or congestive heart failure (CHF, n = 4) as determined by clinical and contractile performance parameters. RESULTS: Substantial reductions in steady-state mRNA expression for ANT1 and betaF1 relative to normal (n = 8) occur in CHF, p < 0.01, but not in LVR. Relative expression for both proteins coordinated with their respective steady-state mRNA levels; CHF at 40% normal, p < 0.05 for ANT and 70% normal for betaF1, p < 0.05. CONCLUSIONS: Maintained signaling for major mitochondrial membrane proteins occurs in association with successful remodeling and adaptation after infarction. Reduced expression of these proteins relates to limited ATP synthesis capacity and high energy phosphate kinetic abnormalities previously demonstrated in CHF. These findings imply that mitochondrial processes participate in myocardial remodeling after infarction.

The use of hibernation induction triggers for cardiac transplant preservation.

Cardiac transplant is hindered by donor shortage and preservation time. Extended extracorporeal preservation could increase the number and distribution of hearts for transplantation. Interestingly, mammalian hibernation biology closely parallels the altered cardiac cellular physiology noted with hypothermic organ storage. The present study undertook to test whether treatment with hibernation induction triggers could improve myocardial functional recovery following prolonged ischemic storage in a nonhibernating mammalian model. To study this hypothesis, isolated rabbit hearts had baseline functional and metabolic parameters recorded and then received either hypothermic storage only or standard cardioplegia, or cardioplegia containing 1 mg/kg D-Ala2-Leu5-enkaphalin (DADLE), which mimics natural hibernation, or preperfusion with DADLE, administered for 15 min at 2 mmol, 25 min prior to cardioplegic ischemia. Hearts were then subjected to 18 hr of global ischemic storage at 4 degrees C. Isovolumic developed pressure, coronary flows, and myocardial oxygen consumption were significantly improved with DADLE pretreatment vs. all groups after storage and reflow. Furthermore, DADLE hearts demonstrated better histological ultrastructure preservation following prolonged storage ischemia. This study demonstrates that hibernation protection with DADLE is beneficial for prolonged cardiac storage. The use of hibernation induction triggers is promising for organ preservation and deserve further mechanistic study.

Flavone improves functional recovery after ischemia in isolated reperfused rabbit hearts.

The effects of flavone (2-phenyl-1,4-benzopyrone), a modulator of the cytochrome P-450 monooxygenase system, on myocardial postischemic reperfusion recovery were examined in the present study. Left ventricular functional recovery was evaluated in isolated, crystalloid-perfused rabbit hearts after 2 hours of modestly hypothermic (34 degrees C) global ischemia. Four groups (n = 8 in each group) were studied and compared: a vehicle control group, a second group pretreated with flavone (8 x 10(-6) mol/L) before ischemia, a third group pretreated with flavone followed by SKF 525-A (1.7 x 10(-5) mol/L), an inhibitor of cytochrome P-450, and a fourth group pretreated with flavone followed by indomethacin (1 x 10(-6) mol/L), an inhibitor of cyclooxygenase. At 15, 30, and 45 minutes after reperfusion, recovery of left ventricular developed pressure in the control group averaged (mean +/- standard deviation) only 2.60% +/- 12.7%, 35.5% +/- 15.0%, and 42.9% +/- 13.5% of baseline, respectively. In the flavone-treated group, recovery was significantly better, averaging 67.7% +/- 10.7%, 73.9% +/- 9.3%, and 73.6% +/- 7.6% of baseline at the same time periods. Recovery of peak positive rate of pressure rise in the control group averaged 27.4% +/- 15.2%, 38.6% +/- 19.2%, and 45.4% +/- 18.6% of baseline at 15, 30, and 45 minutes of reperfusion, respectively. In the flavone-treated group recovery values were significantly higher, averaging 67.8% +/- 9.6%, 77.3% +/- 8.5%, and 77.0% +/- 9.0% of baseline. End-diastolic pressures were significantly lower in the flavone-treated group compared with the control group at all reperfusion time points. Myocardial oxygen consumption was significantly higher in the flavone-treated group at 30 and 45 minutes of reperfusion, as well. The improvement resulting from flavone infusion was abolished completely by SKF 525-A, providing support for the interpretation that the effects of flavone were mediated through the cytochrome P-450 system. The cyclooxygenase inhibitor indomethacin midly attenuated the effects of flavone pretreatment, suggesting that the effects of flavone were only minimally related to metabolites of cyclooxygenase. We conclude that pretreatment with flavone represents a promising approach to myocardial protection that may be due to modulation of the myocardial cytochrome P-450 system.

Triiodothyronine repletion in infants during cardiopulmonary bypass for congenital heart disease.

OBJECTIVE: Cardiopulmonary bypass suppresses circulating thyroid hormone levels. Although acute triiodothyronine repletion has been evaluated in adult patients after cardiopulmonary bypass, triiodothyronine pharmacokinetics and effects have not previously been studied in infants undergoing operations for congenital heart disease. We hypothesized that triiodothyronine deficiency in the developing heart after bypass may adversely affect cardiac function reserve postoperatively. METHODS: Infants less than 1 year old undergoing ventricular septal defect or tetralogy of Fallot repair were randomized into 2 groups. Group T (n = 7) received triiodothyronine (0.4 microg/kg) immediately before the start of cardiopulmonary bypass and again with myocardial reperfusion. Control (NT, n = 7) patients received saline solution placebo or no treatment. RESULTS: These groups underwent similar ischemic and bypass times and received similar quantities of inotropic agents after the operation. The NT group demonstrated significant depression in circulating levels, compared with prebypass levels, for free triiodothyronine and total triiodothyronine at 1, 24, and 72 hours after bypass. Group T demonstrated similar low thyroxine values, but free and total triiodothyronine levels were maintained at prebypass levels for 24 hours and remained elevated over those of group NT (P <.05) at 72 hours. Heart rate was transiently elevated in group T compared with group NT (P <.05), and peak systolic pressure-rate product increased after 6 hours. CONCLUSION: These data imply that (1) triiodothyronine in the prescribed dose prevents circulating triiodothyronine deficiencies and (2) triiodothyronine repletion promotes elevation in heart rate without concomitant decrease in systemic blood pressure. Elevation of peak systolic pressure-rate product implies that triiodothyronine repletion improves myocardial oxygen consumption and may enhance cardiac function reserve after cardiopulmonary bypass in infants.

Influence of the pH of cardioplegic solutions on cellular energy metabolism and hydrogen ion flux during neonatal hypothermic circulatory arrest and reperfusion: a dynamic 31P nuclear magnetic resonance study in a pig model.

OBJECTIVES: The pH of cardioplegic solutions is postulated to affect myocardial protection during neonatal hypothermic circulatory arrest. Neither optimization of cardioplegic pH nor its influence on intracellular pH during hypothermic circulatory arrest has been previously studied in vivo. Thus we examined the effects of the pH of cardioplegic solutions on postischemic cardiac function in vivo, including two possible operative mechanisms: (1) reduction in adenosine triphosphate use and depletion of high-energy phosphate stores or (2) reduction of H+ flux during reperfusion, or both. METHODS: Dynamic 31P spectroscopy was used to measure rates of adenosine triphosphate use, high-energy phosphate depletion, cytosolic acidification during hypothermic circulatory arrest, and phosphocreatine repletion and realkalinization during reperfusion. Neonatal pigs in three groups (n = 8 each)--group A, acidic cardioplegia (pH = 6.8); group B, basic cardioplegia (pH = 7.8); and group N, no cardioplegia--underwent hypothermia at 20 degrees C with 60 minutes of hypothermic cardioplegia followed by reperfusion. RESULTS: Recoveries of peak elastance, stroke work, and diastolic stiffness were superior in group B. Indices of ischemic adenosine triphosphate use, initial phosphocreatine depletion rate, and tau, the exponential decay half-time, were not different among groups. Peak [H+] in group A (end-ischemia) was significantly elevated over that of group B. The realkalinization rate was reduced in group B compared with that in groups A (p = 0.015) and N (p = 0.035), with no difference between groups A and N (p = 0.3). Cytosolic realkalinization rate was markedly reduced and the half-time of [H+] decay was increased during reperfusion in group B. CONCLUSIONS: Superior postischemic cardiac function in group B is not related to alterations in ischemic adenosine triphosphate use or high-energy store depletion, but may be due to slowing in H+ efflux during reperfusion, which should reduce Ca++ and Na+ influx.

Glucose level and myocardial recovery after warm arrest.

BACKGROUND: During induced cold ischemia for cardiac operations, increasing glucose concentration is not thought to enhance myocardial protection and may detrimentally affect recovery. However, during "warm aerobic" arrest, increased glucose availability as substrate could enhance postischemic metabolic and functional recovery, as during and after ischemia, myocytes shift preference for substrate from fatty acids to glucose. Unfortunately, hyperglycemia may also increase patient susceptibility to neurologic injury. METHODS: This experiment was designed to study the optimal dose of glucose and its effect on function during warm arrest. Isolated, retrograde-perfused rabbit hearts received multidose cardioplegia containing increasing concentrations of glucose, from 0 to 88 mmol/L, and underwent 120 minutes of "warm" 34 degrees C global ischemia. Osmolarities were adjusted equivalently. RESULTS: After 34 degrees C ischemia, hearts treated with 5 to 88 mmol/L glucose showed significantly better functional recovery than those treated with 0 to 1 mmol/L glucose. However, the addition of 22 mmol/L glucose demonstrated optimal recovery with no further incremental enhancement with more glucose. Additional hearts receiving 0 or 22 mmol/L glucose had high-energy phosphates, lactate, CO2, and pH measured. The 22 mmol/L glucose hearts demonstrated active metabolism and significantly better recovery of high-energy phosphate levels than controls. CONCLUSIONS: Increasing glucose level modestly during warm arrest enhanced recovery, but profound hyperglycemia did not incrementally improve this effect, mandating a cautious use of glucose.

Stunning, preconditioning, and functional recovery after global myocardial ischemia.

Stunning (reversible myocardial ischemia without necrosis) occurs with induced global ischemia during cardiac operations and depresses the ability of the heart to utilize oxygen efficiently because less contractile work is developed per unit of oxygen utilized. Interestingly, regional studies have demonstrated dramatic infarct size reduction with stunning episodes before prolonged ischemia, a phenomenon known as myocardial preconditioning. It is postulated that the postischemic contractile dysfunction noted after stunning causes reduced energy demands, which "preconditions" myocardium to withstand a subsequent longer ischemic episode. Some evidence from regional studies suggests that preconditioning may improve functional recovery after ischemia. This study examined the complex relationship between stunning and preconditioning to functional recovery in a surgical setting of global ischemia. To study the effect of stunning, myocardial oxygen consumption, oxygen extraction, and functional indices of contractility were measured before and after isolated rabbit hearts were subjected to 10, 20, or 45 minutes of normothermic 37 degrees C global ischemic stun intervals. This demonstrated that while oxygen consumption and extraction quickly recover to prestun levels, contractility remains depressed well beyond the stun interval. To study the effect of preconditioning using stunning, isolated hearts were then subjected to 120 minutes of 34 degrees C cardioplegic-induced ischemia after preconditioning. Hearts received either modified St. Thomas cardioplegic solution as a control or cardioplegia administered after preconditioning with 37 degrees C ischemic stunning for 5, 10, 15, 20, or 45 minutes or multiple 5- or 10-minute stuns, with reperfusion before cardioplegic-induced ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

[Changes in systolic and diastolic function of reperfused myocardium after short coronary occlusions in conscious dogs].

Mongrel dogs were chronically implanted with sonomicrometer crystals and a high fidelity tip micromanometer to measure ventricular wall thickness (WT) and left ventricular pressure (LVP), respectively. Two weeks after surgical operation, the left circumflex coronary artery was occluded with a hydraulic occluder for 3 minutes in conscious condition. During reperfusion, the hemodynamic parameters and systolic wall thickening recovered to the normal level quickly, while an abnormal thickening phase during early relaxation (extra phase) appeared in the dWT/dt-WT loop (X-axis = WT, Y-axis = dWT/dt) with its pattern different from that during control and ischemic conditions. This kind of pattern of the loop could be observed during hypoxia and during rapid overfilling of coronary artery. It is supposed that some substances, which may be produced in the ischemic myocardium, induced an extra dilation of coronary artery during reperfusion and a rapid overperfusion in the early relaxation phase of the cardiac cycle, leading to the abnormal pattern in the loop.