Biomedical subjects

L C Tumiati

Publications and source records attributed to L C Tumiati.

At least 19 recordsLinked to original sources

PubMed1999

Optimal myocardial preconditioning in humans.

We developed a model of ischemia and reperfusion (I and R) in human ventricular myocytes (CM). CM injury and metabolics were studied after various interventions: endogenous preconditioning (PC) with anoxia, hypoxia, and anoxic or hypoxic supernatants; endogenous PC with or without SPT or adenosine deaminase; and exogenous adenosine PC before, during, or after I or continuously, with or without SPT. To assess the clinical implications of PC and the possible mediating effects of adenosine, patients undergoing elective coronary bypass surgery (CABG) received either a high or low dose of adenosine. Patients not receiving adenosine served as controls. Adenosine levels, high-energy phosphate levels, the metabolic parameters were evaluated from blood samples and left ventricular biopsy samples. Our cellular model studies indicated that preconditioning conferred protection to human CM via an adenosine-mediated pathway. Adenosine simulated PC without a fall in ATP. Adenosine administered to patients during CABG stimulated myocardial metabolism while preventing the degradation of high energy phosphates. A prospective randomized trial of adenosine administered to high-risk patients for myocardial protection is required.

Adenosine↗

PubMed1998

Optimal myocardial preconditioning in a human model of ischemia and reperfusion.

BACKGROUND: Adenosine (ADE) may mediate the protective effects of preconditioning (PC). However, human data are lacking, and the optimal method of ADE administration and the mechanism of protection remain unresolved. METHODS AND RESULTS: We have developed a model of simulated "ischemia" (I) and "reperfusion" (R) in quiescent human ventricular cardiomyocytes. Cellular injury and metabolic parameters were assessed after various interventions: Cells were preconditioned with anoxia (PC0), hypoxia (PC16), anoxic supernatant (SUP0), or hypoxic supernatant (SUP16) with or without the ADE receptor antagonist (SPT) or ADE deaminase (ADA). ADE was applied before, during, or after I or continuously with and without SPT. Cells were treated with the PKC agonist PMA. PC cells were incubated with the protein kinase-C (PKC) antagonist Calphostin-C (Cal-C). PKC translocation and PKC activity were assessed. PC0 was most protective. Protection was transferable via SUP0, which produced the highest concentrations of ADE. Protection was lost with SPT or ADA. Intracellular ATP fell after PC and prolonged I and R. Exogenous ADE was most protective when administered before I at 50 mumol. ADE during I was partially protective. No additional protection was provided with continuous ADE treatment. ADE prevented ATP degradation but increased lactate immediately after its administration. SPT abolished the protective effects of ADE. PMA conferred protection, which was abolished with Cal-C. ADE stimulated PKC translocation and PKC activity in the absence of SPT. CONCLUSIONS: Maximal I confers maximal PC. The degree of I is reflected in supernatant ADE concentrations. The initial ATP fall with PC may account for a lack of ATP preservation after I and R. ADE reproduces the protective effects of PC, preserves ATP, and increases lactate production, perhaps by stimulating glycolysis. Clinical trials of ADE administered during cardiac surgery are necessary to further define its beneficial effects in humans.

Adenosine↗

PubMed1998

Insulin stimulates pyruvate dehydrogenase and protects human ventricular cardiomyocytes from simulated ischemia.

UNLABELLED: Impaired myocardial metabolism after cardioplegic arrest results in persistent anaerobic lactate production. Insulin may protect the heart from ischemia and reperfusion by enhancing myocardial metabolic recovery. However, the stimulation of glycolysis during ischemia may be detrimental because of an accumulation of metabolic end-products. We examined the effect of insulin on quiescent human ventricular cardiomyocytes subjected to simulated cardioplegic ischemia and reperfusion. METHODS: Primary cardiomyocyte cultures were established from patients undergoing corrective repair of tetralogy of Fallot. Cells were exposed to varying concentrations of glucose and insulin during 30 minutes of stabilization in 10 mL of phosphate-buffered saline solution. Ischemia was simulated by exposing the cells to a low volume (1.5 mL) of deoxygenated phosphate-buffered saline solution for 90 minutes followed by 30 minutes of simulated reperfusion in 10 mL of normoxic phosphate-buffered saline solution. Cell viability was assessed by trypan blue exclusion. The activity of mitochondrial pyruvate dehydrogenase was measured in 3 states: stabilization, ischemia, and reperfusion. In addition intracellular lactate, adenine nucleotides, extracellular lactate, pyruvate, and acid release were measured. RESULTS: Higher ambient glucose concentrations resulted in greater cellular injury although insulin-treated cells displayed less injury after ischemia and reperfusion. Insulin increased the pyruvate dehydrogenase activity by 31% in cardiomyocytes and reduced extracellular lactate production by 40%. Intracellular adenosine triphosphate was improved by 75% in cells exposed to high glucose concentrations in the presence of insulin. CONCLUSIONS: Insulin protected human ventricular cardiomyocytes from ischemia and reperfusion. This protection may be due to a stimulation of pyruvate dehydrogenase activity which resulted in improved aerobic metabolism.

Adenine Nucleotides↗

PubMed1998

Preconditioning human cardiomyocytes and endothelial cells.

BACKGROUND: The effects of simulated "ischemia" and "reperfusion" were evaluated in cell cultures of human ventricular cardiomyocytes and human saphenous vein endothelial cells. METHODS: Myocyte and endothelial cell cultures were exposed to a low volume (1.5 ml) of either hypoxic (oxygen tension = 16 mm Hg) or anoxic (oxygen tension = 0 mm Hg) phosphate-buffered saline solution for 90 minutes ("ischemia") followed by 30 minutes of simulated "reperfusion." Cell injury was evaluated by trypan blue exclusion. Next, the effects of a preconditioning stimulus were evaluated by a brief (10 minute) exposure to hypoxic or anoxic ischemia and 10 minutes of reperfusion before prolonged (90 minutes) anoxic ischemia. Finally, the effects of anoxic preconditioning on intracellular lactate accumulation and extracellular lactate and acid release were assessed. RESULTS: "Ischemia" and "reperfusion" resulted in greater injury to endothelial cells than to cardiomyocytes. In both cell types, anoxic ischemia resulted in greater injury than hypoxic ischemia. Preconditioning reduced cell injury in myocytes but not in endothelial cells. Endothelial cells produced more lactate than cardiomyocytes under normoxic conditions. Ischemia increased lactate accumulation and release in cardiomyocytes but not endothelial cells. Preconditioning reduced lactate accumulation and release in cardiomyocytes but not endothelial cells. CONCLUSIONS: Endothelial cells were more susceptible to the same period of simulated ischemia than cardiomyocytes. Preconditioning protected cardiomyocytes but not endothelial cells from a subsequent prolonged period of ischemia and reperfusion.

Cell Hypoxia↗

PubMed1998

Myocardial aerobic metabolism is impaired in a cell culture model of cyanotic heart disease.

A human pediatric cardiomyocyte cell culture model of chronic cyanosis was used to assess the effects of low oxygen tension on mitochondrial enzyme activity to address the postoperative increase in lactate and decreased ATP in the myocardium and the high incidence of low-output failure with restoration of normal oxygen tension, after technically successful corrective cardiac surgery. Chronically hypoxic cells (PO2 = 40 mmHg for 7 days) exhibited significantly reduced activities for pyruvate dehydrogenase, cytochrome-c oxidase, succinate cytochrome c reductase, succinate dehydrogenase, and citrate synthase. The activity of NADH-cytochrome c reductase was unaffected. Lactate production and the lactate-to-pyruvate ratio were significantly greater in hypoxic cardiomyocytes. Western and Northern analysis demonstrated a decrease in the levels of various mRNA and corresponding polypeptides in hypoxic cells. Thus hypoxia influences mitochondrial metabolism through acute and chronic adaptive mechanisms, reflecting allosteric (posttranscriptional) and transcriptional modulation. Transcriptional downregulation of key mitochondrial enzyme systems can explain the insufficient myocardial aerobic metabolism and low-output failure in children with cyanotic heart disease after cardiac surgery.

Adenosine Triphosphate↗

PubMed1996

Human pediatric and adult ventricular cardiomyocytes in culture: assessment of phenotypic changes with passaging.

OBJECTIVES: The purpose of this study was to assess morphologically and biochemically the phenotypic changes which occur in vitro with passaging of human pediatric and adult ventricular cardiomyocytes. METHODS: Human ventricular cardiomyocytes from 3 children (1 to 2 years of age) and an adult patient (65 years of age) undergoing open heart surgery and an adult heart transplant patient (55 years of age) were isolated, cultured, purified, and passaged. Growth curves and 3H-thymidine uptake studies were performed. Characterization of the cells was done by light microscopy, transmission electron microscopy, immunofluorescent staining for myoglobin, CK-MB, and cardiac-specific troponin I isoform, human ventricular myosin heavy chain (HVMHC) and light chain 1 (HVMLC1), Northern blot analysis of HVMHC, and CK-MB activity and mass measurements. Passage 3 cardiomyocyte and pediatric myocardial phospholipids were analysed by gas chromatography. RESULTS: Pediatric cells were smaller (P < 0.01) and divided faster (P < 0.001, ANOCOVA) than adult cells. The cardiomyocytes showed phenotypic changes in primary culture with essentially complete loss of sarcomeres by 10 days and a gradual loss of myofilaments with passaging. The cells were identified as cardiomyocytes by immunohistochemistry for myoglobin, CK-MB, cardiac-specific troponin I isoform, HVMHC and HVMLC1, and by Northern blot analysis for the 3'-end of HVMHC mRNA. The composition of phospholipid fatty acids in the cultured pediatric cells was similar to that found in the pediatric myocardium. CK-MB activity and mass could be measured in the cardiomyocytes. The adult cardiomyocytes were more difficult to maintain than the pediatric cells which could be cultured for as long as 6 months. CONCLUSIONS: Primary cultures of human pediatric and adult partially differentiated ventricular cardiomyocytes can be passaged. Although rapid disorganization of the myofibrils occurs, the non-contractile cells can be identified as cardiomyocytes by morphological appearance, immunofluorescent staining, Northern blot analysis for HVMHC, and CK-MB activity.

Actin Cytoskeleton↗

PubMed1995

Tepid antegrade and retrograde cardioplegia.

To determine the optimal temperature for the combination of antegrade and retrograde cardioplegia, 42 patients undergoing coronary artery bypass grafting were randomized to receive cold (9 degrees C; n = 14), tepid (29 degrees C; n = 14), or warm (37 degrees C; n = 14) blood cardioplegia delivered continuously retrograde and intermittently antegrade. Myocardial oxygen utilization, lactate and acid metabolism, and coronary vascular resistance were measured during the operation and cardiac function was assessed postoperatively. Myocardial oxygen consumption, lactate release and acid release were greatest with warm, intermediate with tepid, and least with cold cardioplegia (p = 0.0001). However, washout of lactate and acid at the time of cross-clamp release was reduced (p = 0.022) with tepid or cold compared with warm cardioplegia. Early postoperative left ventricular function was best preserved (p = 0.01) after tepid than after cold or warm combination cardioplegia. These results suggest that tepid combination cardioplegia reduced metabolic demands but permitted immediate recovery of cardiac function. This technique may provide better myocardial protection than cold or warm combination cardioplegia.

Aged↗

PubMed1995

Cardiac storage with University of Wisconsin solution and a nucleoside-transport blocker.

Findings from previous investigations conducted at this institution and others have suggested that University of Wisconsin solution (UWS) is preferable for the prolonged hypothermic storage of hearts before transplantation. The benefit seen with UWS may in part be related to the inclusion of adenosine (5 mmol/L) in the UWS. To investigate whether further manipulations of adenosine metabolism might enhance myocardial protection, studies were initially conducted using cultured myocytes, followed by confirmatory experiments using isolated rat hearts. Cultured human ventricular myocytes (7 to 8 dishes/group) were stored for 12 hours at 0 degrees C in unmodified UWS or UWS supplemented with increasing concentrations (1 to 100 mumol/L) of the nucleoside-transport blocker p-nitrobenzylthioinosine. The adenosine triphosphate concentrations were found to be enhanced with nucleoside-transport inhibition, with the best results achieved with the 1- and 3-mumol/L groups (control, 3.37 +/- 0.41 nmol/micrograms DNA; UWS, 2.89 +/- 1.31 nmol/micrograms DNA; 1 mumol/L, 5.91 +/- 3.23 nmol/micrograms DNA; 3 mumol/L, 7.86 +/- 3.45 nmol/micrograms DNA; p < 0.05 versus control or UWS group). Isolated rodent hearts from Sprague-Dawley rats were prepared on a Langendorff apparatus with an intraventricular balloon and subsequently stored for 8 hours at 0 degrees C in unmodified UWS (13 hearts/group) or UWS supplemented with 1 or 3 mumol/L of p-nitrobenzylthioinosine (9 to 10 hearts/group).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

PubMed1995

Adequate distribution of warm cardioplegic solution.

Seventy-five patients undergoing coronary artery bypass grafting were randomized to receive warm antegrade (N = 25), warm retrograde (N = 25), or a combination of warm antegrade and retrograde (N = 25) delivery of blood cardioplegic solution. Myocardial oxygen utilization, lactate and acid metabolism, and adenine nucleotides and their degradation products were measured during the operation and cardiac function was assessed postoperatively. Warm retrograde delivery of cardioplegic solution increased lactate and acid release during cardioplegia and reperfusion, decreased left ventricular adenosine triphosphate concentrations, and reduced the washout of adenine nucleotide degradation products from both left and right ventricles. Warm antegrade delivery of cardioplegic solution resulted in less lactate and acid release during cardioplegia but more lactate accumulated in the territory of the left anterior descending artery during the crossclamp period. Intermittent antegrade delivery of the cardioplegic solution during combination cardioplegia washed out lactate and acid, which suggested inhomogeneous delivery of the cardioplegic solution during continuous retrograde cardioplegia. Combination cardioplegia best preserved adenosine triphosphate in the left ventricle and resulted in the best postoperative left and right ventricular function. A combination of intermittent antegrade and continuous retrograde delivery of cardioplegic solution provided better myocardial protection than either antegrade or retrograde delivery of cardioplegic solution alone.

Adenine Nucleotides↗

PubMed1994

The optimal cardioplegic temperature.

Seventy-two patients undergoing coronary artery bypass grafting were randomized to receive cold (8 degrees C) antegrade or retrograde, tepid (29 degrees C) antegrade or retrograde, or warm (37 degrees C) antegrade or retrograde blood cardioplegia (n = 12 in each group). Myocardial oxygen utilization as well as lactate and acid metabolism were assessed intraoperatively and cardiac function was assessed postoperatively. Myocardial oxygen consumption and anaerobic lactate release were greatest during warm, intermediate during tepid, and least during cold cardioplegic arrest. Myocardial oxygen consumption and lactate release were underestimated during retrograde cardioplegia because of contamination of aortic root samples. Warm retrograde and tepid retrograde cardioplegia resulted in greater lactate and acid washout with reperfusion. Left ventricular stroke work indices were greater after warm antegrade and tepid antegrade cardioplegia than after cold antegrade cardioplegia, and right ventricular stroke work indices were greatest after warm antegrade cardioplegia. Warm antegrade cardioplegia increased aerobic metabolism during and after cardioplegia and preserved left and right ventricular function. Tepid antegrade cardioplegia reduced anaerobic lactate and acid release during arrest and preserved cardiac function.

Adult↗

PubMed1994

Preconditioning human ventricular cardiomyocytes with brief periods of simulated ischaemia.

OBJECTIVE: The aim was to test for "ischaemic" preconditioning in monolayer cultures of quiescent human ventricular cardiomyocytes. METHODS: Stabilised cardiomyocytes (n = 8 plates per group) were preconditioned with varying periods of simulated ischaemia and reperfusion, followed in all groups by 90 min of sustained "ischaemia" with or without 30 min of reperfusion. Cellular injury was assessed by trypan blue exclusion and survival was assessed by culturing the cells for 24 h postintervention. In addition, separate groups of cell plates (n = 8 per group) which had first been preconditioned with 20 min ischaemia and 20 min reperfusion were exposed to either 30, 60, or 90 min sustained ischaemia or 90 min sustained ischaemia with 30 min reperfusion. The supernatants and/or cell homogenates were analysed for hydrogen ion, lactate, lactate dehydrogenase (LDH), and adenine nucleotides and degradation products. RESULTS: Preconditioning (PC) decreased trypan blue uptake following subsequent sustained ischaemia, with the 20 min ischaemia/20 min reperfusion (20/20) regimen having the most profound effect [control ischaemia: 37.0(SEM 2.1); 10/10: 23.9(1.5); 20/20: 15.4(1.4); 30/30: 25.8(2.1) percent blue stained cells, p < 0.05 by ANOVA/Duncan]. The 20/20 preconditioning regimen resulted in less hydrogen ion [control: 2.1(0.4); PC: 1.4(0.1) mmol.g-1 protein, p < 0.05] and less LDH release [control: 20.7(3.1); PC: 11.9(4.2) units.g-1 protein, p < 0.05]. At 90 min of sustained ischaemia, the control group had produced significantly greater lactate [intracellular: control 1.55(0.62); PC 0.54(0.23) mol.g-1 DNA, p < 0.05; extracellular: control 0.47(0.09); PC 0.33(0.07) mol.g-1 DNA, p < 0.05]. There were no differences in ATP depletion in the two groups. CONCLUSIONS: Ischaemic preconditioning can be induced in human cardiomyocytes independent of other cell types. The effect can be established in human cell cultures.

Cells, Cultured↗

PubMed1993

Comparison of two experimental models for assessment of cardiac preservation.

Previous studies from this institution using human cell cultures have suggested that University of Wisconsin solution is preferred for prolonged hypothermic storage for cardiac transplantation. The primary objective of this study was to evaluate the effectiveness of extended cardiac preservation with University of Wisconsin solution by assessing the time-related changes of purine metabolites using two different models of cold storage. Isolated rat hearts (n = 6/group) or human ventricular myocyte cultures (n = 7 dishes/group) were assessed after 0, 6, 12, and 24 hours in University of Wisconsin solution at 0 degrees C using high-performance liquid chromatography. Adenosine triphosphate content decreased from 18.1 +/- 5.4 to 9.6 +/- 2.7 mumol/g dried weight by 12 hours and to 1.0 +/- 0.6 mumol/g by 24 hours (p < 0.0001 by analysis of variance) in the rat model. Adenosine triphosphate content decreased from 0.64 +/- 0.42 to 0.14 +/- 0.11 nmol/micrograms DNA at 6 hours and to 0.04 +/- 0.03 nmol/micrograms DNA by 24 hours (p < 0.00001) in the cardiomyocytes. Inosine monophosphate content increased from 0.1 +/- 0.2 to 10.8 +/- 1.0 by 24 hours (p < 0.0001) in the rat studies. Inosine monophosphate values tended to increase up to 12 hours (p = 0.06) in the cell cultures and then declined. Adenosine concentration increased from 0.3 +/- 0.3 to 2.3 +/- 0.9 mumol/g at 6 hours and declined thereafter (p < 0.0005) in the rodent hearts. Adenosine concentration increased from 0.03 +/- 0.02 to 1.53 +/- 0.72 nmol/micrograms DNA at 6 hours (p < 0.0001) in the cardiomyocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1993

Which techniques of cardioplegia prevent ischemia?

One hundred seven patients undergoing coronary artery bypass grafting were randomized to receive warm antegrade (n = 21), warm retrograde (n = 22), cold antegrade (n = 20), cold retrograde (n = 22), or intermittent cold antegrade (n = 22) blood cardioplegia. Myocardial oxygen consumption and lactate production, adenine nucleotides, and adenine nucleotide degradation products were measured during the operation, and creatine kinase-MB release was assessed postoperatively. Warm cardioplegia resulted in greater myocardial lactate production than cold cardioplegia (p = 0.048). Retrograde cardioplegia was associated with greater lactate production than antegrade cardioplegia (p = 0.015). Adenosine triphosphate depletion was similar among groups. However, poorly diffusible metabolites of adenosine triphosphate accumulated to the greatest extent in the intermittent cold group. Levels of hypoxanthine were highest after warm retrograde cardioplegia. Operative mortality and morbidity were low and were not different among groups. In summary, none of the five techniques of cardioplegia evaluated in this study was able to completely prevent myocardial ischemia. Anaerobic lactate production was minimized with cold cardioplegia and with antegrade cardioplegic delivery. Hypothermia may have impaired regeneration of adenosine triphosphate, however, particularly in association with inadequate or intermittent cardioplegic flow.

Adenosine Monophosphate↗

PubMed1992

Prolonged hypothermic cardiac storage for transplantation. The effects on myocardial metabolism and mitochondrial function.

Cardiac storage for transplantation is currently limited to 6 hours. To better understand the metabolic changes that occur during hypothermic (4 degrees C) storage, we monitored the morphologic and metabolic changes in the canine myocardium at 0, 12, and 24 hours of storage in University of Wisconsin solution. Attempts to isolate cardiac mitochondria resulted in a progressive decline in the yield (milligrams of mitochondria per gram of heart tissue), which decreased (p less than 0.05) from 9.2 +/- 0.4 at 0 hours (control) to 4.0 +/- 0.3 after 12 hours and further decreased (p less than 0.05) to 1.9 +/- 0.2 after 24 hours of cold storage. Mitochondrial state 3 respiration fell to 64% of control after 12 hours and 28% of control after 24 hours of cold storage (p less than 0.05). Citrate synthetase activity, but not cytochrome C oxidase activity, was significantly depressed after 12 and 24 hours of cold storage. Adenosine triphosphate content decreased to 67% of control after 12 hours and 50% of control after 24 hours. After 12 hours of storage, sufficient adenosine diphosphate and monophosphate were present to permit some restoration of adenosine triphosphate, provided mitochondrial function was normal after transplantation. However, restoration of mitochondrial function and adenosine triphosphate levels sufficient to support myocardial contractility was unlikely after 24 hours of storage. This study suggests that a return of adequate cardiac function after transplantation may be possible after 12 hours of cold storage in University of Wisconsin solution but not after 24 hours of cold storage.

Adenosine Triphosphate↗

PubMed1992

In vitro assessment of the effects of glucose added to the University of Wisconsin solution on myocyte preservation.

BACKGROUND: University of Wisconsin solution (UWS) has been successfully used for liver transplantation and may be beneficial for hypothermic cardiac storage. The addition of glucose may enhance myocardial preservation. METHODS AND RESULTS: Cultured human ventricular myocytes (eight dishes per group) were stored at 0 degree C for 12 hours in either unmodified UWS or UWS with glucose (1, 3, 10, 30, or 100 mmol/l). Cells were assayed for protein by spectrofluorometry and adenine nucleotides by high performance liquid chromatography after storage. Protein recovery, adenosine triphosphate (ATP), adenosine diphosphate (ADP), and total adenine nucleotides (ATP+ADP+AMP) were all depleted after storage (p < 0.0001 by ANOVA). Protein recovery (p < 0.005), ATP (p < 0.05), and ADP (p < 0.05) were increased with glucose administration compared with unmodified UWS. Improvement was maximal using 30 mmol/l (protein, 0 mmol/l = 0.48 +/- 0.14 and 30 mmol/l = 0.65 +/- 0.11 mg per dish; ATP, 0 mmol/l = 3.08 +/- 0.63 and 30 mmol/l = 4.32 +/- 0.90 nmol/mg protein; ADP, 0 mmol/l = 3.76 +/- 0.80 and 30 mmol/l = 4.63 +/- 0.38 nmol/mg protein, mean +/- SD). Total adenine nucleotides tended to increase at any glucose concentration (p = 0.07 by ANOVA) and were significantly better with 30 mmol/l glucose (0 mmol/l = 7.61 +/- 1.58 and 30 mmol/l = 9.62 +/- 1.08 nmol/mg protein). CONCLUSIONS: Increasing the glucose concentration from 0 to 30 mmol/l improved adenine nucleotide and cellular protein preservation in this in vitro assessment.

Adenine Nucleotides↗

PubMed1992

Alternative techniques of cardioplegia.

BACKGROUND: Although normothermic cardioplegia has been used with acceptable clinical results, no studies have previously been performed to determine the metabolic consequences of these various techniques of myocardial protection. Therefore, we have performed a randomized clinical trial to assess the effects of three cardioplegic techniques on myocardial metabolic recovery. METHODS AND RESULTS: Seventy-four patients undergoing coronary artery bypass graft surgery were randomized to receive normothermic antegrade blood cardioplegia (n = 25), normothermic retrograde blood cardioplegia (n = 23), or intermittent cold antegrade blood cardioplegia (n = 26). Myocardial oxygen consumption and lactate production, adenine nucleotides, and adenine nucleotide degradation products were measured during the operation, and cardiac creatine kinase isoenzyme (CK-MB) release was assessed after surgery. Warm antegrade cardioplegia maximized myocardial oxygen consumption during cardioplegic delivery. Postoperative CK-MB release was less after warm antegrade cardioplegia, but the difference was not statistically significant. Warm retrograde cardioplegia resulted in the greatest degree of anaerobic lactate production but did not increase morbidity and mortality. Perioperative myocardial infarctions and postoperative low-output syndrome were most common after cold cardioplegia, but this trend was not statistically significant. During warm antegrade cardioplegia, adenosine triphosphate (ATP) was metabolized to diffusible precursors, which were washed out during cardioplegic infusion. Warm retrograde cardioplegia produced a breakdown of ATP to inosine and hypoxanthine, small molecules that accumulated during the cross-clamp period and were not washed out, perhaps because of inadequate perfusion with retrograde delivery. During cold cardioplegia, ATP was dephosphorylated, and adenosine diphosphate, adenosine monophosphate, and adenosine accumulated. These compounds were not regenerated to ATP but were not washed out of myocytes because they are large anionic molecules. CONCLUSIONS: Intermittent cold cardioplegia inhibited mitochondrial function but prevented the degradation of adenine nucleotides. Warm antegrade cardioplegia had the greatest myocardial oxygen consumption, and warm retrograde cardioplegia had the greatest anaerobic lactate production. There were no differences in clinical outcomes between cardioplegic groups.

Adenosine Triphosphate↗

PubMed1992

Effect of oxygen tension and cardiovascular operations on the myocardial antioxidant enzyme activities in patients with tetralogy of Fallot and aorta-coronary bypass.

Since the chronically cyanotic myocardium appears to be more susceptible to reperfusion injury after cardiac operations than the noncyanotic myocardium, we studied the association between the preoperative arterial oxygen tension and the myocardial superoxide dismutase, catalase, and glutathione peroxidase activities. Fourteen patients with tetralogy of Fallot scheduled for elective operations had baseline arterial blood gas measurements done before operation. During the operation right ventricular biopsy specimens were taken for enzyme analysis immediately before cold blood cardioplegic arrest and 20 minutes after crossclamp removal. The tissue antioxidant enzyme activities of the patients with tetralogy of Fallot were compared with the myocardial results in 15 adults with stable angina pectoris having elective aorta-coronary artery bypass graft operations. Myocardial tissues removed from two patients with hypertrophic obstructive cardiomyopathy who had corrective operations were analyzed for antioxidant activities. There were no changes in myocardial antioxidant enzyme activities during the operation in the patients with tetralogy of Fallot and coronary artery bypass graft. The myocardial superoxide dismutase, catalase, and glutathione peroxidase activities correlated (0.82, 0.68, and 0.89, respectively) significantly (p values were less than 0.01, 0.05, and 0.01, respectively) with the preoperative arterial oxygen tensions in the patients with tetralogy of Fallot. The myocardial glutathione peroxidase activities were at least four times higher in the myocardium of patients with coronary artery bypass graft and hypertrophic obstructive cardiomyopathy than in that of those with tetralogy of Fallot. This study provides putative evidence that the myocardium of patients with tetralogy of Fallot is a risk of oxygen-derived free radical injury during and immediately after corrective cardiovascular operations.

Catalase↗

PubMed1991

The limits of cardiac preservation with University of Wisconsin solution.

Previous studies from this institution have suggested that University of Wisconsin solution is preferred for prolonged cardiac storage and preserves high-energy phosphates better than other storage fluids. University of Wisconsin solution contains adenosine (5 mmol/L), which may maintain the concentration of myocardial adenine nucleotides. Cultures of human adult myocytes were grown from left ventricular biopsy specimens obtained from patients undergoing coronary bypass procedures. Cells (seven to nine dishes per group) were rinsed of culture medium and stored at 0 degrees C in University of Wisconsin solution. Cells were analyzed for adenine nucleotide content after 1, 6, 12, and 24 hours of storage by high-performance liquid chromatography (units = nmol/microgram DNA) and compared with control samples (0 hour). Adenosine concentration increased from 0.03 +/- 0.02 (mean +/- standard deviation) to 1.77 +/- 1.03 by 1 hour (p less than 0.0001, analysis of variance) and remained increased thereafter. Adenosine was largely degraded to inosine (0 hours, 0.03 +/- 0.03; 6 hours, 0.88 +/- 0.56; p less than 0.001) and hypoxanthine (0 hours, 0.01 +/- 0.01; 6 hours, 0.15 +/- 0.09; p = 0.004). Measured levels of xanthine and uric acid were extremely low at all time intervals. Adenosine triphosphate levels were maintained at 1 hour (0 hours, 0.64 +/- 0.38; 1 hour, 0.67 +/- 0.45) but declined thereafter (6 hours, 0.21 +/- 0.21; 12 hours, 0.11 +/- 0.09; 24 hours, 0.04 +/- 0.03; p less than 0.0001). Levels of adenosine diphosphate (p = 0.007) and adenosine monophosphate (p less than 0.05) decreased to approximately 25% of original values by 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗