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Subunits VIIa,b,c of human cytochrome c oxidase. Identification of both 'heart-type' and 'liver-type' isoforms of subunit VIIa in human heart.

The N-terminal amino acid sequences and the electrophoretic mobilities of the subunits VIIa, VIIb and VIIc of cytochrome c oxidase purified from human heart were investigated and compared with those from human skeletal muscle and from bovine heart. In purified human heart cytochrome c oxidase, both so-called 'heart-type' and 'liver-type' isoforms of subunit VIIa were found. The first 30 residues of the N-terminal amino acid sequences of these 'heart-type' and 'liver-type' subunits VIIa showed nine differences. The two isoforms of subunit VIIa in human heart were present in almost equal amounts, in contrast to the situation in skeletal muscle, where the 'heart-type' subunit VIIa was predominant. Therefore, our results imply that in human heart a cytochrome c oxidase isoform pattern is present that differs from that found in skeletal muscle. Subunits VIIb and VIIc purified from human heart oxidase proved to be very similar to their bovine heart counterparts. Our direct demonstration of the presence of subunit VIIb, the sequence of which has only recently been identified in the bovine heart enzyme, suggests that human cytochrome c oxidase also contains 13 subunits. We found no evidence for the presence of different isoforms of subunit VIIc in cytochrome c oxidase from human heart and skeletal muscle. We observed clear differences in the electrophoretic mobility of the subunits VIIa,b,c between bovine and human cytochrome c oxidase. On Tricine/glycerol/SDS/polyacrylamide gels the 'heart-type' and 'liver-type' subunits VIIa present in human heart cytochrome c oxidase migrated with almost the same electrophoretic mobility. Subunit VIIb migrated only slightly faster than subunit VIIa, whereas VIIc proved to have the highest electrophoretic mobility on Tricine/SDS/glycerol/polyacrylamide gels. Our findings may have implications for the elucidation of certain tissue-specific cytochrome c oxidase deficiencies in man.

Amino Acid Sequence↗

Cardiac troponin I is a heart-specific marker in the Xenopus embryo: expression during abnormal heart morphogenesis.

Cardiac troponin I (troponin Ic) expression is restricted to the heart at all stages of Xenopus development. Whole-mount in situ hybridization and Northern blot analysis indicates that troponin Ic is first expressed in tailbud embryos (stage 28) about the time of the first cytological heart differentiation and about 24 hr before beating tissue is observed. We have used this marker to examine abnormal heart morphogenesis in embryos treated with retinoic acid and lithium. When retinoic acid is administered to embryos prior to heart specification, heart tissue is reduced and often completely ablated. When embryos are treated after heart specification, but before the heart primordium migrates to the ventral midline, the migration is unaffected but smaller, abnormal hearts result. Lithium treatment of cleavage stage embryos causes an increase in heart tissue. In severely dorsalized embryos, heart tissue can be found around the entire embryo with the exception of a small gap at the most dorsal point. This gap indicates that migration of the heart to the ventral midline does not occur in these embryos. Later in development, a centrally located, beating heart is observed in dorsalized embryos. The timing of its appearance suggests that it is formed by movements normally associated with heart morphogenesis rather than migration.

Animals↗

ATPase activity, IF1 content, and proton conductivity of ESMP from control and ischemic slow and fast heart-rate hearts.

Earlier studies by Rouslin and coworkers showed that, during myocardial ischemia in slow heart-rate species which include rabbits and all larger mammals examined including humans, there is an IF1-mediated inhibition of the mitochondrial ATPase due to an increase in the amount of IF1 bound to the ATPase (Rouslin, W., and Pullman, M.E., J. Mol. Cell. Cardiol. 19,661-668, 1987). Earlier work by Guerrieri and colleagues demonstrated that IF1 binding to bovine heart ESMP was accompanied by parallel decreases in ATPase activity and in passive proton conduction (Guerrieri, F., et al., FEBS Lett. 213, 67-72, 1987). In the present study rabbit was used as the slow heart-rate species and rat as the fast heart-rate species. Rat is a fast heart-rate species that contains too little IF1 to down regulate the ATPase activity present. Mitochondria were prepared from control and ischemic hearts and ESMP were made from aliquots by sonication at pH 8.0 with 2 mM EDTA. Oligomycin-sensitive ATPase activity and IF1 content were measured in SMP prepared from the control and ischemic mitochondrial samples. After identical incubation procedures, oligomycin-sensitive ATPase activity, oligomycin-sensitive proton conductivity, and IF1 content were also measured in ESMP samples. The study was undertaken to corroborate further what appear to be fundamental differences in ATPase regulation between slow and fast heart-rate mammalian hearts evident during total myocardial ischemia. Thus, passive proton conductivity was used as an independent measure of these regulatory differences. The results show that, consistent with the low IF1 content of rat heart cardiac muscle mitochondria, control rat heart ESMP exhibit approximately twice as much passive proton conductivity as control rabbit heart ESMP regardless of the pH of the incubation and assay. Moreover, while total ischemia caused an increase in IF1 binding and a commensurate decrease in passive proton conductivity in rabbit heart ESMP regardless of pH, neither IF1 content nor proton conductivity changed significantly in rat heart ESMP as a result of ischemia.

Adenosine Triphosphate↗

[Status of intensified therapy and regionalized allocation of donor hearts in the management of patients with terminal heart failure].

BACKGROUND AND OBJECTIVE: The medical management of heart failure improved greatly during the last decade. Heart transplantation (HTx) as surgical alternative is an established measure but operation numbers stagnated due to the lack of donor organs and still the 1 year mortality is about 20%. Rising numbers of new registrations led to long waiting lists with a high mortality rate. Solutions are intensified therapeutic concepts and improvements in organ allocation. This study was done to show if a combined intensified medical management and a regional donor allocation system may improve outcome in heart transplant candidates. PATIENTS AND METHODS: A cohort of 396 elective candidates for heart transplantation from the years 1984-1997 without contraindications and at least in NYHA stage III at entry were investigated for total mortality, modes of death and the probability of heart transplantation. Patients were divided in two groups (group A: submitted from 1984-1994, n = 256, group B: 1995-1998, n = 150). RESULTS: The groups were comparable in clinical and hemodynamic baseline characteristics. Patients of group B had a better long-term prognosis after 2 years (87% versus 73.5%, p = 0.009) and had a significantly lower rate of heart transplantation (HTx rate in group A and B after 2 years: 35% and 15%, p = 0.002). Only two patients died due to heart failure in the years 1995-1998 compared to 20 heart failure death from 1984-1994. The waiting time for a donor heart fell from 81.8 +/- 80 days in group A to 22.1 +/- 21 days in group B. The main problem is the unchanged sudden death rate in patients with stable hemodynamics prior to the event. CONCLUSIONS: A combination of tailored medical therapy for heart failure plus regionalization of donor heart allocation with short waiting time seems to be the best way to treat patients with end-stage heart failure. A specialized cardiomyopathy program is necessary for such an approach. Sudden death in heart transplant candidates has to be studied more intensively.

Adult↗

Plasma endothelin concentrations in humans with end-stage heart failure and after heart transplantation.

OBJECTIVES AND BACKGROUND: Endothelin is an endothelium-derived vasoconstrictor peptide that increases systemic and renal vascular resistance at pathophysiologic concentrations. Recent studies have demonstrated its presence in the circulation and its elevation in animals with congestive heart failure, suggesting that endothelin may contribute to the vasoconstrictive state of heart failure. The current study was designed with two objectives: 1) to demonstrate the elevation of circulating endothelin in patients with heart failure, and 2) to determine the short- and long-term response of endothelin levels after heart transplantation. METHODS: Plasma endothelin concentrations were measured in two patient groups. Group 1 included 24 patients with end-stage heart failure who were studied during evaluation for potential heart transplantation. Group 2 included 12 patients from Group 1 who had had heart transplantation. Plasma endothelin concentrations were measured before and on days 1, 3 and 7 after heart transplantation. Eight of these patients also had levels measured 3 to 12 months later. RESULTS: Plasma endothelin concentrations were significantly elevated in patients with heart failure compared with those in an age-matched control group (11.7 +/- 1.1 vs. 6.8 +/- 0.3 pg/ml). In response to heart transplantation, plasma endothelin concentrations increased further and were sustained during a long-term follow-up. These later changes were associated with a significant increase in arterial pressure and serum creatinine. CONCLUSIONS: This study demonstrates that endothelin concentrations are increased in patients with heart failure and increase further after heart transplantation. It suggests a possible role for endothelin in the cardiovascular and renal adaptive responses to human heart transplantation.

Blood Pressure↗

Successful heart transplantation after 13 hours of donor heart ischemia with the use of HTK solution: a case report.

INTRODUCTION: For heart transplantation (HTx), the recommended ischemic time (IT) for donor heart is not to exceed 6 hours. Though Dr Christiaan Barnard used a donor heart with IT of 16 hours, 50 minutes with a portable hypothermic perfusion system in 1981, the recorded IT of donor hearts reported recently is 8 hours, with no adverse effects. CASE REPORT: The patient, a 14-year-old boy of blood type O, was diagnosed with cardiomyopathy at age 12. In early September 2003, the patient was recommended for HTx. His condition deteriorated 18 days later with low CO, elevated pulmonary vascular resistance, and frequent ventricular tachycardia, further complicated by pneumonia and multiorganism infections, which were contraindications for HTx. On September 22, 2003, a donor heart of blood type O was available 370 km away. Another patient of blood type B with severe heart failure was matched for the HTx. During the intervening time, another donor heart of blood type B became available locally. We matched the type B donor heart to the type B recipient. Since the type O donor heart seemed to be wasted, we performed HTx for the boy. Though preserved for 12 hours in cold cardioplegia, the donor heart was implanted with biatrial anastomosis that took 1 hour. The total IT of this donor heart was 13 hours. The recipient recovered and was discharged 3 months later. CONCLUSIONS: The IT of 13 hours for this donor heart is believed to be a world record. Our experience demonstrates that preservation time of donor heart may exceed 6 hours.

Adolescent↗

Effect of mibefradil on heart rate variability in patients with chronic heart failure.

BACKGROUND: Mibefradil was recently withdrawn from the market because of an unfavorable clinical profile in patients with chronic heart failure. Although drug interactions appear to play a role, other mechanisms such as proarrhythmia and autonomic deterioration could also be relevant. Chronic heart failure is accompanied by autonomic impairment and analysis of heart rate variability can be used to examine autonomic modulation of heart rate. METHODS: We studied 18 heart failure patients (age 63.2+/-10.1 years (mean+/-S.D. ), ejection fraction 0.21+/-0.07) treated with mibefradil or placebo, who participated in the MACH-I (Mortality Assessment in Chronic Heart failure) trial in our center, and compared them with 18 healthy matched controls. Heart rate variability analysis was performed at baseline and after 7 months of treatment. RESULTS: At baseline, heart rate variability parameters were impaired in patients with heart failure compared to healthy controls (P<0.05). After 7 months of treatment a reduction in (24-h) heart rate was observed (P=0.02, versus placebo). Apart from the effect on mean NN, no significant differences were observed for the remaining heart rate variability parameters. CONCLUSIONS: Mibefradil does not impair autonomic balance and in fact reduces heart rate in patients with heart failure. These findings suggest that autonomic activation did not contribute to the adverse effects of mibefradil.

Autonomic Nervous System↗

Respiratory-related heart rate variability in progressive experimental heart failure.

Heart failure is associated with autonomic imbalance, and this can be evaluated by a spectral analysis of heart rate variability. However, the time course of low-frequency (LF) and high-frequency (HF) heart rate variability changes, and their functional correlates during progression of the disease are not exactly known. Progressive heart failure was induced in 16 beagle dogs over a 7-wk period by rapid ventricular pacing. Spectral analysis of heart rate variability and respiration, echocardiography, hemodynamic measurements, plasma atrial natriuretic factor, and norepinephrine was obtained at baseline and every week, 30 min after pacing interruption. Progressive heart failure increased heart rate (from 91 +/- 4 to 136 +/- 5 beats/min; P < 0.001) and decreased absolute and normalized (percentage of total power) HF variability from week 1 and 2, respectively (P < 0.01). Absolute LF variability did not change during the study until it disappeared in two dogs at week 7 (P < 0.05). Normalized LF variability increased in moderate heart failure (P < 0.01), leading to an increased LF-to-HF ratio (P < 0.05), but decreased in severe heart failure (P < 0.044; week 7 vs. week 5). Stepwise regression analysis revealed that among heart rate variables, absolute HF variability was closely associated with wedge pressure, right atrial and pulmonary arterial pressure, left ventricular ejection fraction and volume, ratio of maximal velocity of early (E) and atrial (A) mitral flow waves, left atrial diameter, plasma norepinephrine, and atrial natriuretic peptide (0.45 < r < 0.65, all P < 0.001). In tachycardia-induced heart failure, absolute HF heart rate variability is a more reliable indicator of cardiac dysfunction and neurohumoral activation than LF heart rate variability.

Animals↗

Abnormalities in baroreflex control of heart rate in canine heart failure.

The mechanism of the attenuated arterial baroreceptor control of heart rate in heart failure was studied in 18 unanesthetized dogs after the development of chronic right-heart failure and compared to 12 control animals. The change in heart rate and arterial pressure in response to increases in right carotid sinus pressure during isolated carotid sinus perfusion was markedly reduced in heart failure (P less than 0.05). After vagotomy the difference in heart rate responses persisted, but was less pronounced (P = 0.065). The chronotropic response to perfusion of the sinus node artery with acetylcholine in heart-failure dogs showed a selectively depressed response, when compared to norepinephrine and hypertonic saline. The ratio of the change in heart rate in heart-failure vs. control dogs was 57% for acetylcholine but was not diminished for hypertonic saline (114%). The effect of direct vagal nerve stimulation on changes in heart rate was also markedly reduced in heart-failure dogs. These studies demonstrate that the alterations in baroreceptor control of heart rate in heart failure involve both the parasympathetic and sympathetic baroreflex efferent limbs. There is, in addition, a depressed responsiveness of the sinus node to cholinergic stimuli.

Animals↗

Independent association between plasma leptin levels and heart rate in heart transplant recipients.

BACKGROUND: Leptin, the protein product of the ob gene, has been linked to a faster heart rate in animal and human studies. The interaction between leptin and heart rate in the denervated heart is not known. Therefore, we studied the relationship between plasma leptin levels and heart rate in heart transplant recipients. METHODS AND RESULTS: We studied 32 male patients (mean age, 56.5+/-9.3 years; range, 41 to 74 years) after orthotopic heart transplantation. All subjects underwent a physical examination, anthropometric measurements, blood chemistry analysis, and office blood pressure measurements. A blood sample was collected from each subject while fasting. In univariate analysis, heart rate was related to leptin levels (r=0.47, P=0.007) but heart rate was not related to systolic or diastolic blood pressure, mean arterial pressure, body mass index, or catecholamines. Leptin levels were only strongly associated with heart rate and body mass index (r=0.73, P<0.0001). In multivariate analysis, heart rate was independently and positively associated with leptin levels (F=2.61, P=0.017). We also observed a strong, independent association between leptin levels and body mass index (F=5.8, P<0.00001). CONCLUSIONS: We show an independent association between leptin levels and heart rate in heart transplant recipients. We speculate that this may be due, in part, to a direct effect of leptin on heart rate, conceivably mediated through cardiac leptin receptors.

Adult↗

The effect of ATP-sensitive potassium channel modulation on heart rate in isolated muskrat and guinea pig hearts.

Muskrats (Ondontra zibethicus) are common freshwater diving mammals exhibiting a bradycardia with both forced and voluntary diving. This bradycardia is mediated by vagal innervation; however, if hypoxia is present there may be local factors that also decrease heart rate. Some of these local factors may include ATP-sensitive potassium channel activation and extracellular accumulation of potassium ions, hydrogen ions and lactate. The purpose of this study was to investigate the role of these factors in the isolated perfused hearts of muskrats and of a non-diving mammal, the guinea pig. Although lactate and proton administration reduced heart rate in isolated muskrat and guinea pig hearts, there was no difference in the response to lactate and proton infusion between the two species. Muskrat hearts were more sensitive to the heart-rate-lowering effects of exogenously applied potassium than were guinea pig hearts. Early increases in extracellular potassium concentration during hypoxia are thought to be mediated by the ATP-sensitive potassium channel. Activation of these channels under normoxic conditions had a mildly negative chronotropic effect in both species; however, activation of these channels with Lemakalim under hypoxic conditions caused the guinea pig heart to respond with an augmented bradycardia similar to that seen in the hypoxic muskrat heart in the absence of drugs. Inhibition of these channels by glibenclamide during hypoxia was partially successful in blocking the bradycardia in guinea pig hearts, but inhibition of the same channels in hypoxic muskrat hearts had a damaging effect as two of five hearts went into contracture during the hypoxia. Thus, although ATP-sensitive potassium channels appear to have a major role in the bradycardia of hypoxia in guinea pigs, the failure to prevent the bradycardia by inhibition of these channels in muskrat hearts suggests that multiple factors are involved in the hypoxia-induced bradycardia in this species.

Adenosine Triphosphate↗

Increased circulating calcitonin gene-related peptide in congestive heart failure caused by congenital heart disease.

Calcitonin gene-related peptide has potent vasodilatory and inotropic actions. The aim of this study was to characterize the changes in this peptide in children with varying degrees of heart failure secondary to congenital heart disease with left to right shunt and to assess its relationship to systolic pulmonary arterial pressure. Plasma calcitonin gene-related peptide levels were measured in 131 children including 13 healthy ones, 43 with various degrees of heart failure secondary to congenital heart disease, and 75 with congenital heart disease without heart failure. In patients with heart failure, calcitonin gene-related peptide concentrations were markedly elevated (15.8 +/- 2.1 pg/mL) as compared with healthy control subjects (7.0 +/- 0.8 pg/mL, P < 0.05) or patients with congenital heart disease but without heart failure (18.6 +/- 1.2 pg/mL, P < 0.01). Compared with the controls, there were highly significant stepwise increases in the calcitonin gene-related peptide levels in the mild (n = 15), moderate (n = 12), and severe (n = 16) heart failure subgroups by 1.5, 1.7 and 3.4 fold, respectively. The plasma calcitonin gene-related peptide levels also correlated directly with the pulmonary arterial systolic pressure (r = 0.515, P < 0.0001). The results of this study indicate that congestive heart failure secondary to congenital heart disease with increased pulmonary flow is associated with elevated levels of calcitonin gene-related peptide that are related to disease severity. Pulmonary overcirculation may play a role in upregulation of calcitonin gene-related peptide in congestive heart failure.

Blood Pressure↗

Electrocardiography, heart rates, and heart weights of free-living birds.

To examine the waveforms of electrocardiograms, cardiac rhythm, heart rates at rest and during excitement, and the rate of increase of heart rate, electrocardiograms were recorded with standard bipolar limb leads from 79 free-living birds, including 19 species. The heart weights and heart-to-body weight ratios were obtained from an additional 96 free-living birds, including 20 species. In the majority of the electrocardiograms, lead I was of low amplitudes for all waves except the P wave, and leads II and II were very similar to each other with a predominant S wave and a very short or elevated ST segment. The P wave was often superimposed on the T wave when the heart rate increased to 330 beats/min. Four types of arrhythmia were observed in 50 of the 79 birds (63.3%): 48 sinus arrhythmias, four sinus arrests, two atrial premature contractions, and one ventricular premature contraction. The resting heart rate was negatively associated with the rate of increase, suggesting that a bird with a low resting rate might be able to maintain a greater capacity to increase its heart rate than one with a high resting rate. A negative correlation on a bilogarithmic scale was obtained between the heart weight and the resting heart rate, indicating that a bird with a high heart weight had lower resting heart rate than a bird with a low heart weight. When the heart-to-body weight ratios of free-living birds were compared according to their motility, the ratios of more active birds were greater than those of less active ones.

Animals↗

Evaluation of ventricular myocardial velocities and heart motion of the fetal heart by tissue Doppler image.

UNLABELLED: Fetal echocardiogram has developed into a reliable tool for prenatal diagnosis of congenital heart disease. It is also used to evaluate ventricular function. Recently, Tissue Doppler Imaging (TDI) has been introduced to evaluate ventricular functions especially in ischaemic heart disease. The objective of this study was to evaluate myocardial velocities and heart motions of the normal fetal heart by using TDI. The TDI was preformed in 28 fetal hearts with a gestational age of 20-35 wks (Mean 29 +/- 3.7 wks) to evaluate myocardial velocities and heart motion. The Toshiba, Power Vision, machine with 3.75 and 5 MHz transducers was used with an appropriate setting of colour-coded tissue velocities. The apical four chamber and apical or parasternal long axis views were the standard planes for measuring myocardial velocities and evaluating the heart motions. The results showed the myocardial velocities of the posterior wall of the left ventricle during the early, mid, and late systolic phases were 1.5 +/- 0.2, 2.1 +/- 0.9, and 1.0+0.5 cm/sec and early, mid, and late diastolic phases were 1.3 +/- 0.7, 1.9 +/- 0.8, and 1.1 +/- 0.7 cm/sec respectively. The myocardial velocity of the anterior wall of the right ventricle during the early, mid, and late systolic phases were 1.7 +/- 0.9, 1.7 +/- 0.6, and 1.0 +/- 0.6 cm/sec and early, mid, and late diastolic phases were 1.1 +/- 0.6, 1.8 +/- 0.7, and 1.5 +/- 1.0 cm/sec respectively. The myocardial velocity of the interventricular septum could not be measured due to the abnormal septal motion and the total fetal heart movement during the cardiac cycle. The fetal heart had anterior displacement during systole and posterior translation during diastole and also had counter-clockwise rotation during the systolic phase. CONCLUSION: Using the TDI to evaluate myocardial velocities of the fetal heart is limited by the angle of ultrasound beam and the total fetal heart motion. The fetal heart movement is similar to the newborn or young adult heart.

Adult↗

Graft coronary disease in pediatric heart and combined heart-lung transplant recipients: a study of fifteen cases.

Graft coronary disease (GCD) has emerged as the most important deterrent to long-term survival in adult heart transplant recipients. The incidence, natural history, and pathobiology of GCD is less well understood in the pediatric transplant population. This study evaluated the histopathologic and immunohistochemical features of GCD in the Stanford pediatric heart and heart-lung group. Eighty-eight patients, ages 1 week to 18 years, received heart transplants between 1974 and 1992, and 15 patients, ages 1 month to 18 years received heart-lung transplants between 1981 and 1992 at Stanford University Hospital. There were 50 males and 38 females in the heart transplant group; 39 (11%) had idiopathic cardiomyopathy, 26 (30%) had congenital heart disease, 13 (15%) had viral cardiomyopathy, seven (8%) had familial cardiomyopathy, two (2%) had cardiomyopathy resulting from doxorubicin therapy, and one other case was not further delineated. In the heart-lung transplant group, there were eight males and seven females; pretransplantation diagnoses included nine (60%) with congenital heart disease and Eisenmenger's physiology, three (20%) with primary pulmonary hypertension, and one (7%) each with cystic fibrosis, bronchopulmonary dysplasia, and congenital lymphangiectasia. Fifteen (17%) of the heart transplant recipients and three (20%) of the heart-lung transplant recipients had GCD on angiographic or pathologic examination. Histopathologic samples were available on 14 cases (11 heart transplants and three heart-lung transplants).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Heterotopic heart transplantation: catheterization, endomyocardial biopsy, and coronary angiography of the donor heart.

UNLABELLED: Follow-up after heart transplantation presently requires invasive techniques to assess graft viability and function. As the heterotopic transplant technique assumes a more important therapeutic role for patients not eligible for an orthotopic allograft, an understanding of the inherent challenges associated with management of these patients is mandatory to optimize patient care. Heterotopic transplant technique was used in 19 of 135 (14%) consecutive heart transplant procedures over a 41 month period. Invasive diagnostic procedures performed in follow-up revealed 1) adequate tissue for histologic evaluation in 140/158 (89%) biopsy procedures, 2) successful pulmonary wedge pressure measurements in 142/158 (90%) right heart catheterizations, and 3) successful coronary arteriography in 18 patients undergoing angiography (both vessels in 12 and one vessel in six patients). Thus, biopsy and surveillance procedures are feasible and productive in patients who have undergone heterotopic heart transplantation. BACKGROUND: Although heterotopic heart transplantation has become an increasingly utilized therapy for some patients with heart failure, there are no guidelines for routine biopsy and angiographic techniques in these patients. The objective of this study was to determine the feasibility of angiographic and endomyocardial biopsy procedures in heterotopic heart transplant recipients. METHODS: The complete experience with heterotopic heart transplant recipients at Baylor College of Medicine and The Methodist Hospital over a 41 month period including endomyocardial biopsy, right heart catheterization, and selective coronary arteriography results were analyzed. RESULTS: Eighteen patients underwent 310 procedures without significant complications. Of 158 biopsy procedures, 140 (89%) yielded tissue adequate for histologic evaluation. Right heart pressures were obtained in almost all patients undergoing right heart catheterization. Pulmonary wedge pressures were obtained in 137 (90%). A rapid decrease in right heart pressures was noted following transplant; however, a gradual but significant rise in mean arterial pressure occurred. Eighteen selective coronary arteriogram procedures were performed; 12 (66%) resulted in successful cannulation of both coronary arteries. Of 12 patients followed for at least 1 year, five (40%) have developed evidence of allograft arteriopathy. The 1 and 2 year survival rates were 67% and 53%, respectively. CONCLUSIONS: Invasive diagnostic techniques can be performed safely and reliably and should not preclude the use of heterotopic heart transplantation in selected patients who are otherwise unsuitable for orthotopic transplantation.

Biopsy↗

Myocardial viability twenty-four hours after orthotopic heart transplantation from non-heart-beating donors.

OBJECTIVES: Using a new preservation strategy, we investigated the performance of hearts from non-heart-beating donors during an observation period of 24 hours after orthotopic heart transplantation in a pig model. METHODS: In the control group (n = 6) beating donor hearts were harvested with Bretschneider's HTK solution and transplanted orthotopically without reperfusion modifications. In the non-heart-beating donor group (n = 6) hearts were perfused with leukocyte-depleted blood cardioplegia after 30 minutes of normothermic ischemia. Blood cardioplegia was supplemented with a sodium-hydrogen exchange inhibitor and adenosine. After transplantation, a second controlled reperfusion with blood cardioplegia was performed. RESULTS: Preload recruitable stroke work of the left ventricle 24 hours after transplantation in the control versus non-heart-beating donor group was 108% +/- 24% versus 103% +/- 18% of baseline values. Myocardial blood flow of the left and right ventricle was increased to 146% +/- 32% and 176% +/- 51% in the control group versus 176% +/- 29% and 194% +/- 27% in the non-heart-beating donor group. Myocardial oxygen consumption was 11.2 +/- 2.1 versus 12.8 +/- 2.2 mL/100 g per minute at baseline and 11.6 +/- 2.6 versus 13.2 +/- 3.1 mL/100 g per minute after 24 hours (not significant). Histologic examination with Luxol fast blue staining revealed that 2.6% +/- 4.8% of myocytes in the control group versus 1.8% +/- 1.9% in the non-heart-beating donor group were damaged irreversibly. CONCLUSIONS: Recovery of donor hearts from non-heart-beating donors is comparable with recovery of organs harvested from heart-beating donors if the above-mentioned preservation technique is used. These results could encourage the use of marginal donor hearts and help to expand the limited donor pool.

Animals↗

The impact of central lung distance, maximal heart distance, and radiation technique on the volumetric dose of the lung and heart for intact breast radiation.

PURPOSE: To investigate the impact of radiographic parameter and radiation technique on the volumetric dose of lung and heart for intact breast radiation. METHODS AND MATERIALS: Forty patients with both two-dimensional (2D) and computed tomographic (CT) simulations were enrolled in the study. Central lung distance (CLD), maximal heart distance (MHD), and maximal heart length (MHL) were measured under virtual simulation. Four plans were compared for each patient. Plan A used a traditional 2D tangential setup. Plan B used clinical target volume (CTV) based three-dimensional (3D) planning. Both plans C and D used a combination of a medial breast field with shallow tangents. Plan D is a further modification of plan C. RESULTS: Under the traditional tangential setup, the mean ipsilateral lung dose and volume at 20, 30, and 40 Gy correlated linearly with CLD (R = 0.85 approximately 0.91). The mean ipsilateral lung dose (Gy) approximated 4 times the CLD value (cm), whereas the percentage volume (%) of ipsilateral lung at 20, 30, and 40 Gy was about 10 times the CLD (cm). The mean heart dose and percentage volume at 20, 30, and 40 Gy correlated with MHD (R = 0.76 approximately 0.80) and MHL (R = 0.65 approximately 0.75). The mean heart dose (Gy) approximated 3 times the MHD value (cm), and the percentage volume (%) of the heart at 10, 20, 30, and 40 Gy was about 6 times MHD (cm). Radiation technique impacted lung and heart dose. The 3D tangential plan (plan B) failed to reduce the volumetric dose of lung and heart from that of the 2D plan (plan A). The medial breast techniques (plans C and D) significantly decreased the volume of lung and heart receiving high doses (30 and 40 Gy). Plan D further decreased the 20 Gy volumes. By use of the medial breast technique, the lung and heart dose were not impacted by original CLD and MHD/MHL. Therefore, the improvement from the tangential technique was more remarkable for patients with CLD >or= 3.0 cm (p < 0.001). CONCLUSIONS: The CLD and MHD impact the volumetric dose of lung and heart. The application of 3D planning for tangential breast irradiation does not decrease heart and lung dose. Adding a medial breast port significantly decreases percentage volume (PV) of lung and heart receiving high doses, especially when the CLD is excessive.

Breast Neoplasms↗