Biomedical subjects

R D Weisel

Publications and source records attributed to R D Weisel.

At least 19 recordsLinked to original sources

PubMed1992

Production and reversibility of right ventricular hypertrophy and right heart failure in dogs.

Combined heart-lung transplantation has been used for end-stage primary pulmonary hypertension. Experience with single-lung transplantation for other conditions suggested that associated severe right ventricular dysfunction resulting from increased afterload would recover after placement of a satisfactory lung allograft. Early experience with the application of single-lung transplantation for pulmonary hypertension supports this contention. We devised a reversible canine model of chronic progressive pressure-overloaded right heart failure by pulmonary artery banding to study the echocardiographic, hemodynamic, and pathological reversibility of the failing right heart. Clinical right heart failure was defined as the development of ascites and pleural effusions. Right heart failure developed in 23 dogs 67 to 348 days after banding, and they were divided into two groups to determine its early and long-term effects. Group 1 dogs (n = 11) were either sacrificed immediately after the onset of right heart failure (n = 5) or unbanded (n = 6); group 2 dogs (n = 12) were maintained in right heart failure for 3 months and then either sacrificed (n = 6) or unbanded. Unbanded dogs in both groups were observed for 4 additional months before sacrifice. A control group of 6 normal dogs was sacrificed for pathological comparisons. After unbanding, the right ventricular systolic pressure fell from 97 +/- 17 mm Hg (group 1) and 88 +/- 31 mm Hg (group 2) to 44 +/- 11 mm Hg and 47 +/- 13 mm Hg, respectively. Despite this persistent gradient across the pulmonary artery, echocardiographic and hemodynamic measures of right ventricular function returned to normal, albeit more slowly in the group 2 dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

The regulation of glutathione peroxidase gene expression by oxygen tension in cultured human cardiomyocytes.

In earlier studies we have shown that the activity of the antioxidant enzyme glutathione peroxidase is regulated by oxygen tension in cultured tetralogy of Fallot (TOF) ventricular myocytes and in the ventricles of TOF patients having corrective cardiac surgery. The present study was undertaken to determine the mechanism of this regulation. Northern and slot blot analysis was performed using RNA isolated from TOF myocytes cultured at oxygen tensions of 150 and 40 mmHg for 3, 7, 14, 21, and 28 days. As was found for enzyme activities, glutathione peroxidase mRNA levels were lower in the cells cultured at a pO2 of 40 mmHg than at 150 mmHg and could be elevated with an increase in oxygen tension. These results were standardized against house-keeping gene hexosaminidase B which showed no difference in mRNA levels between the two oxygen tensions throughout the time course. Nuclear run-off assays indicated that glutathione peroxidase was regulated by oxygen tension at the transcriptional level, while hexosaminidase B and total mRNA synthesis levels remained unchanged.

Adult↗

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

Coronary artery bypass grafting in patients with poor ventricular function. Cardiovascular Surgeons of the University of Toronto.

Although patients with severe ventricular dysfunction have improved long-term survival times after coronary bypass procedures, operative morbidity and mortality rates remain high. This study was designed to identify the contemporary risk factors for isolated coronary artery bypass grafting in this high-risk subgroup. Between January 1982 and December 1990, a total of 12,471 patients underwent isolated coronary artery bypass grafting. The 9445 patients with preoperative ejection fractions greater than 40% had a lower operative mortality rate (2.3%) than that of the 2539 patients with ejection fractions between 20% and 40% (4.8%) and that of the 487 patients with ejection fractions less than 20% (9.8%; p less than 0.001). However, patients with ejection fractions of less than 20% were demographically distinct from those with higher ejection fractions. This group was older, with fewer women, a higher frequency of left main stenosis, and more frequent requirement of urgent operation for unstable angina. The risk factors for operative death also varied with preoperative ejection fraction. The traditionally accepted risk factors--urgency of operation, left main coronary artery stenosis, reoperation, sex, and age--were predictive of risk of operative death for patients with ejection fractions greater than 40%. The risk of operative death for patients with ejection fractions between 20% and 40% was predicted by urgency of operation, reoperation, sex, myocardial protection, and age. The only predictor of risk of operative death for patients with ejection fractions less than 20% was urgency of operation. Patients undergoing isolated coronary artery bypass grafting who have severe ventricular dysfunction are therefore a highly selected, high-risk subgroup of patients who risk depends on the urgency of operation. Strategies to improve the results in these patients should be focused on patient selection, improvement of myocardial protection, and more aggressive preoperative treatment of myocardial ischemia.

Age Factors↗

PubMed1992

The effect of warm heart surgery on postoperative bleeding.

The effects of normothermic systemic perfusion (35 degrees to 37 degrees C; n = 73) were compared with those of moderately hypothermic systemic perfusion (25 degrees to 29 degrees C; n = 73) with respect to blood loss, transfusion requirements, and platelet levels in 146 patients undergoing isolated, primary coronary artery bypass grafting. In addition, most patients were given an antifibrinolytic medication during operation as follows: tranexamic acid (10 gm intravenously; n = 63), epsilon-aminocaproic acid (15 gm intravenously; n = 63), or no drug as a control. (n = 20). Normothermic patients tended to bleed less at 24 hours (warm, 864 +/- 42 ml and cold, 918 +/- 68 ml), but these differences were not statistically significant. Patients receiving either tranexamic acid or epsilon-aminocaproic acid, regardless of perfusion temperature, bled less after 6, 12, and 24 hours than did cold control patients (p less than 0.05). Warm control patients also bled less than did cold control patients after 6 or 12 hours (p less than 0.05), and neither drug further reduced blood loss in these patients. Circulating platelet levels were better preserved in patients receiving either tranexamic acid or epsilon-aminocaproic acid and in patients with warm perfusion and no drug than in cold control patients. Normothermic systemic perfusion, tranexamic acid, and epsilon-aminocaproic acid each reduced postoperative blood loss and preserved platelets.

Aminocaproic Acid↗

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

Effect of orally administered alpha-tocopheryl acetate on human myocardial alpha-tocopherol levels.

Free radical injury may contribute to the delayed postoperative recovery of myocardial metabolism and ventricular function after elective coronary artery revascularization. This clinical study was designed to evaluate, in stable angina patients having aortocoronary bypass surgery, whether orally administered alpha-tocopheryl acetate was effective in increasing myocardial alpha-tocopherol levels and the effect of cardioplegic arrest followed by reperfusion on the myocardial alpha-tocopherol levels. Twenty-four patients with stable angina pectoris for elective revascularization received preoperatively the natural stereoisomer of alpha-tocopheryl acetate labelled with deuterium (D3) and six patients were used as controls. Since four patients who received 300 mg of D3-alpha-tocopheryl acetate preoperatively for 1 and 2 days did not have significant increases in their myocardial total or D3-tocopherol levels, the remaining 20 patients received 100 mg (n = 6), 300 mg (n = 8), or 900 mg (n = 6) of D3-alpha-tocopheryl acetate for 14 consecutive preoperative days. The left ventricular deuterated and nondeuterated alpha-tocopherol levels were measured by gas chromatography/mass spectrometry. Although there was a decrease (p less than 0.05) in myocardial alpha-tocopherol levels with the onset of reperfusion (cross-clamp removal), the myocardial tocopherol levels were not statistically different from preoperative levels by 20 minutes of reperfusion. At least 300 mg of alpha-tocopherol must be taken orally for 14 consecutive days to double the myocardial alpha-tocopherol levels.

Administration, Oral↗

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↗

PubMed1991

Survival and valve failure after aortic valve replacement.

A prospective evaluation of 412 consecutive patients undergoing isolated aortic valve replacement between January 1982 and December 1985 was performed in an attempt to identify the determinants of survival and valve failure. A variety of valves were inserted to permit a prospective evaluation of alternative valves including: Björk-Shiley mechanical (n = 37), Ionescu-Shiley pericardial (n = 261), Hancock pericardial (n = 78), and Carpentier-Edwards porcine (n = 36). Thirteen patients died in the hospital (3.2%) and 47 patients died in the follow-up period producing an actuarial survival of 81% +/- 3% at 48 months. Survival was independently predicted by advancing age, preoperative New York Heart Association functional class, and the presence of endocarditis (p less than 0.05 by Cox regression analysis). The majority of patients were symptomatically improved (New York Heart Association class I or II: 21% preoperative, 88% postoperative). Freedom from structural valve dysfunction, prosthetic valve endocarditis, and reoperation for valve-related complications were 95% +/- 2%, 95% +/- 2%, and 92% +/- 2% at 48 months, respectively. These valve-related complications occurred more frequently in younger patients and in those with a Hancock pericardial valve (freedom from structural valve dysfunction, 89% +/- 5%; prosthetic valve endocarditis, 84% +/- 9%; reoperation, 78% +/- 10%; p less than 0.05 by Cox regression). Freedom from thromboembolism was 88% +/- 2% at 48 months; it was significantly lower in patients with a preoperative thromboembolic event and was not influenced by the type of prosthesis inserted. Freedom from anticoagulant-related hemorrhage was 85% +/- 8% at 48 months and was not influenced by any preoperative factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve↗

PubMed1991

Radiochemical quantitation of conjugated dienes during ischemia and reperfusion in the rat liver.

Conjugated dienes (CD) are putative chemical imprints of oxyradical damage. Employing a highly selective assay for dienes based on their condensation with 14C-tetracyanoethylene (14C-TCNE), and a 14C-TCNE reagent with 60 times higher specific radioactivity than that used by Waller and Recknagel (1978), we have described the profile of phospholipid CD during global ischemia and reperfusion of the rat liver. During 70 min of ischemia, the hepatic CD appeared to increase moderately, but not statistically significantly, relative to that in sham-operated controls (with mean CD = 0.0397 +/- 0.0040 nmoles CD/nmole phosphate, for n = 7). In subsequent reperfusion, CD increased 2.6-3.3 fold higher than in sham controls during the first 10-15 min, declining thereafter to ischemia-like levels by 30 min of reflow. Our data demonstrate that oxyradicals are generated mostly during reperfusion of the post-ischemic rat liver, and that the refined TCNE method can quantitate tissue CD sensitively and relatively specifically.

Alkenes↗

PubMed1991

Prolonged preservation with University of Wisconsin Solution.

Previous studies from this institution using human cell cultures have suggested that University of Wisconsin Solution may be preferred for prolonged cardiac storage. University of Wisconsin Solution (UWS) contains adenosine (5 mmole/liter) which could maintain adenine nucleotides better than other storage fluids. Human cardiomyocytes were isolated from left ventricular biopsies. Cells (seven to nine dishes/group) were rinsed of culture media and placed in one of four solutions: Stanford cardioplegia, phosphate-buffered saline, modified EuroCollins', or UWS. Metabolites were assessed using high-performance liquid chromatography (units = nmole/micrograms DNA) after 24 hr of storage at 0 degrees C and compared to baseline controls (BASE). Adenosine triphosphate (P less than 0.0001, ANOVA), adenosine diphosphate (P less than 0.0001), and adenosine monophosphate (P less than 0.01) decreased with each solution compared to BASE but were maintained best with UWS (P less than 0.05). Adenosine increased in the UWS cells only (BASE, 0.029 +/- 0.118; UWS, 1.836 +/- 1.110; P less than 0.0001, ANOVA). Adenosine in the UWS cells was largely degraded to inosine (UWS, 1.013 +/- 0.779; BASE, 0.034 +/- 0.032; P less than 0.0001) and hypoxanthine (UWS, 0.124 +/- 0.091; BASE, 0.005 +/- 0.005; P less than 0.001). University of Wisconsin Solution does preserve adenine nucleotides better than other storage fluids and may improve the clinical results of cardiac transplantation.

Adenine Nucleotides↗

PubMed1991

Current risk of coronary bypass for unstable angina.

The risk associated with surgical revascularization for unstable angina is critically dependent upon the clinical presentation of the patient. For this study, between January 1982 and December 1987, clinical, angiographic, operative and hospital outcome data were collected prospectively for 6539 patients undergoing surgery for unstable angina. Urgent surgery was performed in 1523 patients (23.3%), while 5016 (76.7%) underwent semielective revascularization. The mean age was 58.9 +/- 9.2 years and 805 patients (12.3%) were aged 70 years or above. The male:female ratio was 3.6:1. Depressed left ventricular function (left ventricular ejection fraction less than 40%) was present in 27.2% of the population. Preoperative myocardial infarction (within 30 days of surgery) had occurred in 588 patients (9.0%). Operative mortality was 4.6% (301 deaths). Stepwise logistic regression analysis was performed to determine the independent predictors of operative mortality. The following variables were selected in descending order: urgent surgery (P less than 0.001), coronary reoperation (P less than 0.001), depressed left ventricular (P less than 0.001), female gender (P less than 0.001), increasing age (P less than 0.001), left main stenosis (P = 0.002), and preoperative myocardial infarction (P less than 0.001). Predicted operative mortality varied between 0.5 +/- 0.3% and 82.6 +/- 12.7%. The most important determinant for patients with a preoperative myocardial infarction was left ventricular dysfunction, whereas urgent surgery for unstable angina was the most important risk variable in those without preoperative necrosis.

Adult↗

PubMed1991

Recent preoperative myocardial infarction increases the risk of surgery for unstable angina.

Patients with postinfarction angina undergoing surgery for unstable angina face an increased risk of operative mortality. Between January 1982 and December 1987, clinical, angiographic, and operative data was collected prospectively in 588 unstable patients with a prior myocardial infarction within 30 days of surgery (MI) and 5951 unstable patients without preoperative damage (NONMI). MI patients were characterized as being older (age greater than or equal to 70 years: MI, 19.7%; NONMI, 11.6%; p less than 0.001) and having more left ventricular dysfunction (left ventricular ejection fraction less than 40%: MI, 34.8%; NONMI, 26.4%; p less than 0.001). Semi-elective surgery was performed in 82.0% of NONMI patients while 76.9% of MI patients underwent urgent surgery. Operative mortality was increased in MI patients (MI, 11.1%; NONMI, 4.0%; p less than 0.001) which was related to the extent of preoperative MI (non-Q wave, 8.3%; Q wave, 17.5%; p less than 0.001). Stepwise logistic regression analysis identified preoperative MI as an independent risk variable of operative mortality for unstable angina. Separate multivariate analyses were performed to identify the independent predictors for MI and NONMI patients. The multivariate predictors of operative death for MI patients were left ventricular dysfunction, reoperative coronary surgery, nonuse of the internal mammary, age, transmural MI (relative risk 2.11 vs non-Q wave infarction) and left main stenosis. For NONMI patients, the independent variables were urgent operation, left ventricular dysfunction, reoperation, female gender, left main stenosis, and age. The results of this study indicate that recent preoperative MI adversely influences the surgical results in patients with unstable angina. Alternative treatment strategies are warranted for high risk patients, particularly those with transmural MIs and impaired ventricular function.

Adult↗

PubMed1991

Thoracic aortic surgery.

Between 1982 and 1989, 119 patients had repair of thoracic aortic pathology. Thirty-seven had repair of ascending aortic aneurysms, with an 11% hospital mortality. Forty-one patients had urgent repair of acute type A aortic dissections, with a 32% hospital mortality. The independent predictors of mortality were the use of crystalloid cardioplegia, aortic dissection, and the use of an intraluminal prosthesis or the inclusion surgical technique. Better grafts and the resection technique has reduced mortality since 1986. Seventeen patients had their primary pathology in the aortic arch, with a 47% hospital mortality. The urgency of the procedure and crystalloid cardioplegia predicted an unsuccessful outcome. Seventeen patients had descending aortic aneurysms repaired, with an 18% mortality. The urgency of surgery was the predictor of mortality. Seven patients had a descending thoracic aortic disruption repaired, with one death (14%). Better graft materials, surgical techniques, and methods of myocardial protection have contributed to the improved results of thoracic aortic surgery in recent years.

Aortic Dissection↗

PubMed1991

Optimal delivery of blood cardioplegia.

A prospective randomized controlled trial was performed to determine optimal flow rates and hemoglobin concentrations for continuous normothermic blood cardioplegia and to compare warm heart surgery with standard intermittent cold blood cardioplegia. Thirty-five patients received intermittent cold blood cardioplegia, low hemoglobin low flow, low hemoglobin high flow, high hemoglobin low flow, or high hemoglobin high flow warm blood cardioplegia (seven patients per group: low hemoglobin, 50 g/l; high hemoglobin, 80 g/l; low flow, less than 80 ml/min; high flow, greater than 80 ml/min). Hypothermia resulted in a significantly greater accumulation of ADP and AMP during cross clamp, consistent with impaired mitochondrial function. Low hemoglobin low flow warm blood cardioplegia increased myocardial oxygen consumption and coronary sinus blood flow after cross clamp release, and also decreased lactate consumption. Postoperative myocardial performance and diastolic compliance were reduced in low hemoglobin low flow warm patients, and diastolic compliance was increased with high hemoglobin high flow warm blood cardioplegia when compared with cold patients. In this study, continuous normothermic cardioplegia was safe when delivered at 80 ml/min or greater, with a hemoglobin concentration of at least 80 g/l, affording myocardial metabolic and functional recovery comparable to that found after intermittent cold blood cardioplegia.

Blood↗

PubMed1991

Prolonged hypothermic cardiac storage with University of Wisconsin solution. An assessment with human cell cultures.

Hypothermic storage of cardiac allografts is routinely used for transplantation but is associated with an increased mortality when ischemic times are greater than 4 hours. The ideal storage conditions (solution and temperature) could extend the current limits of cold ischemia. Human endothelial cells and ventricular myocytes were studied to screen various solutions and temperatures for organ preservation. Four solutions (modified Euro-Collins, phosphate-buffered saline, Stanford cardioplegia, and University of Wisconsin) were evaluated. Endothelial cells were evaluated after prolonged hypothermic storage consisting of 0 degree, 4 degrees, and 8 degrees C for 36 hours, and ventricular myocytes were stored at 0 degree and 8 degrees C for 24 hours. Cell viability was determined by morphology (10 dishes per group), and trypan blue exclusion (5 dishes per group) in addition to a cell adhesion assay (endothelial cells 5 dishes per group) and adenine nucleotide analysis with high-performance liquid chromatography techniques (ventricular myocytes 5 dishes per group). Endothelial cell morphology was best preserved by University of Wisconsin solution (p less than 0.001, chi 2) and at 0 degree C (p less than 0.01, chi 2). Endothelial cells stored with University of Wisconsin solution excluded trypan blue better (1.0% +/- 0.5% cells stained, p less than 0.001. Analysis of variance [ANOVA]). Cell adhesion was poorly protected with Stanford cardioplegia (p less than 0.001, ANOVA). Myocyte morphology was preserved best with University of Wisconsin solution at 0 degree C (p less than 0.001, chi 2). According to trypan blue staining, Euro-Collins and University of Wisconsin solutions were superior to Stanford cardioplegia or phosphate-buffered solutions (p less than 0.001, ANOVA). Temperature did not influence the trypan blue results. Adenosine triphosphate was maintained best with University of Wisconsin solution at 0 degree C (p less than 0.01, ANOVA). Myocytes were more sensitive to the effects of prolonged storage compared with endothelial cells by morphologic criteria and trypan blue staining characteristics, irrespective of the shorter preservation times. University of Wisconsin solution was the most effective solution tested. Colder temperatures (0 degree to 4 degrees C) provided better protection than 8 degrees C. Myocytes were more sensitive to prolonged preservation than endothelial cells. Furthermore, the technique used appears helpful as a model of prolonged hypothermic storage and could be expanded to assess other interventions.

Adenosine Diphosphate↗