Midterm results of free internal thoracic artery grafting for myocardial revascularization.

BACKGROUND: This study investigated the midterm results after free internal thoracic artery (FITA) grafting for coronary artery bypass grafting. METHODS: Between 1988 and 1995, coronary artery bypass grafting and postoperative graft angiography were performed in 337 patients, of whom 56 patients were treated with 57 FITA grafts. We examined the postoperative graft patency of FITA grafts compared with in situ internal thoracic artery (IITA) grafts, and the late results in the patients receiving at least one FITA graft (FITA group) were compared with those in the patients receiving only IITA graft (IITA group). RESULTS: The early postoperative graft patency rate was 93.2% for the FITA grafts and 96.0% for the IITA grafts (not significant [NS]). Patients underwent sequential graft angiography at 29.5 months postoperatively (25 FITA and 89 IITA). The late graft patency rate was 100% and 92.1%, respectively (not significant). The cardiac death-free survival rate at 5 years was 93.5% in the FITA group and 96.6% in the IITA group (not significant), and the angina-free survival rate at 5 years was 80.6% and 83.2%, respectively (not significant). CONCLUSIONS: The FITA provides late results comparable with those attained with IITA.

[Coronary artery bypass surgery in patients older than 70 years of age].

From April 1994 to November 1996, coronary artery bypass grafting (CABG) was performed on 166 patients. Fifty-seven patients were older than 70 years of age (Group A), while 109 were younger than 70 years of age (Group B). In group A, such symptoms as severe stenosis of the left main coronary artery, a history of systemic hypertension, calcification of the ascending aorta, and postoperative respiratory complications with pneumonia were all significantly higher than in Group B. Regarding hospital mortality, the difference between the two groups was not significant. Based on these findings, the use of intensive respiratory care for elderly patients over than 70 years of age is thus considered to help reduce the occurrence of such complications.

Early and late results with combined mitral and aortic valve replacement.

From February 1977 to January 1993, a total of 52 patients have undergone combined mitral and aortic valve replacement (MAVR) at the Fukuoka University Hospital. The ages at operation ranged from 35 to 72 years (mean, 55.3 years) for 16 males and 36 females. Twenty-five patients received two bioprosthetic valves (group BB); 6 received a combination of bioprosthetic valve and mechanical valve (group BM); and 21 received two mechanical valves (group MM). The previous intra-cardiac operations were performed on 24 patients (46.2%). The purpose of this study was to learn about the long-term clinical results of MAVR and to analyze the difference among three groups. Seven patients died within 30 days of operation or during initial hospitalization (early mortality: 13.5%). Two patients died at late period, 5.8 years and 6.9 years after operation, respectively (linearized occurrence rate: 0.9%/pt-yr). Patient survival rate including operative death was 82.9% +/- 5.7% at 5 years and 79.0% +/- 6.7% at 8 years in the total number of patients. Thromboembolism occurred in 2 patients in group MM (0.9%/pt-yr). Anticoagulant-related hemorrhage occurred only in 1 patient (0.4%/pt-yr in overall), in whom two bioprosthetic valves were implanted (group BB), in spite of being in good control with anticoagulants. No infective endocarditis was encountered in any patients during any of the periods. Reoperations were performed in 7 patients (3%/pt-yr in overall), 5 in group BB and 2 in group MM. Percentage freedom from reoperation was 86.4% +/- 5.9% at 5 years and 78.2% +/- 7.7% at 8 years in all. There was no difference among the three groups. Percentage freedom from overall morbidity and mortality was 74.5% +/- 6.9% at 5 years in all. Group MM showed higher morbidity and mortality at 8 years than other groups, but there were no significance (MM: 52.4% +/- 17.6%, BB: 76.5% +/- 9.5%, BM: 83.3% +/- 15.2%). We conclude that there were no significant differences in long-term results of NAVR which consisted of the following combinations of prostheses such as BB, BM, and MM. Redoing MAVR with New York Heart Association functional class IV and emergency cases were considered as in-hospital risk factors.

Influence of superoxide dismutase on reperfusion injury in donor hearts preserved with Bretschneider-HTK cardioplegic solution.

The ability of superoxide dismutase to prevent reperfusion injury after long-term cold storage of donor hearts was evaluated in canine hearts. Whole blood reperfusion was performed using a 'support animal'. Twelve dog hearts were arrested by a single dose of Bretschneider cardioplegic solution and stored cold (0.5 degrees C) for 24 h. Thereafter they were reperfused for 60 min without (n = 6) or with (n = 6) superoxide dismutase treatment. Myocardial tissue biopsies were taken for determination of high-energy phosphates before explantation, after the preservation period and during reperfusion. Early reperfusion in both groups resulted in an initial recovery of high-energy phosphates and was followed by a decrease during the subsequent reperfusion phase. The latter was associated with the appearance of left ventricular contracture, and cessation of heart beat. Electron microscopic examination of the myocardial tissues after reperfusion revealed a severe reperfusion injury in both groups. It is concluded, that in donor hearts preserved with Bretschneider solution, reperfusion injury cannot be prevented by administration via the perfusate of superoxide dismutase.

Left ventricular assistance using a catheter-mounted coaxial flow pump (Hemopump) in a canine model of regional myocardial ischaemia.

The global and regional effects of left ventricular circulatory assistance were examined in dogs during acute myocardial infarction using a new coaxial flow device (Hemopump). In 12 dogs the left anterior descending coronary artery was occluded for 4 h and subsequently reperfused for 12 h. In six dogs, left ventricular assistance was started 90 min after coronary artery occlusion and maintained for several hours; six control animals received no circulatory support. Survival rate in the animals receiving mechanical support was 100% vs 0% in the control group. The Hemopump reduced left ventricular stroke work up to 80% and maintained blood flows to the brain, kidneys, liver and intestine throughout the experiment. Infarct size, expressed as a percentage of the left ventricle, however, was not modified (12% in supported animals vs 13% in control dogs). Side effects of the coaxial flow pump were thrombocytopaenia, occurring in all six dogs, and haemolysis, which was demonstrated in one animal. It was concluded that the Hemopump provides effective global and regional circulatory support in a canine model of severe cardiogenic shock. However, the value of left ventricular support to modify infarct size could not be demonstrated in this experimental model.

Effect of nucleoside transport inhibition on adenosine and hypoxanthine accumulation in the ischemic human myocardium.

The effect of nucleoside transport inhibition on the adenylate catabolism was studied in the human myocardium under normothermic ischemic conditions. Ten hearts from cardiac transplant recipients and two hearts from cardiac homograft donors were used in this study. The hearts were excised under hypothermic conditions (25 degrees C body temperature), the coronary arteries flushed with 500 ml ice-cold Ringer solution (n = 6; group I) or with ice-cold Ringer solution containing 1 mg/l of the nucleoside transport inhibitor R75231 (n = 6; group II). After transportation at 0 degree C from the operation room, the hearts were quickly rewarmed to 37 degrees C. Serial transmural biopsy specimens were taken during normothermic ischemia for determination of purine catabolites. The level of ATP before normothermic ischemia was 17.5 +/- 1.0 mumol/g dry weight in the control group (group I) and 19.3 +/- 0.4 mumol/g dry weight in the drug group. ATP, expressed as percentage of total purine content, was similar in both groups before rewarming (79.5 +/- 4.3% in group I and 79.5 +/- 2.9% in group II). There was no significant difference in the rate of ATP breakdown in both groups throughout the experiment (ATP was 3.0 +/- 1.4% of total purines in group I and 1.4 +/- 0.2% in group II at 120 min of normothermic ischemia). Adenine nucleotide content changed also similarly in both groups. Adenosine accumulation was, however, significantly higher in group II than in group I (peak values: 4.6 +/- 1.0% of total purines in group I vs 14.0 +/- 1.7% in group II; p < 0.01). The ratio between adenosine and inosine was significantly higher in group II throughout normothermic ischemia (p < 0.01). In spite of a larger accumulation of adenosine in group II, the increase in inosine was similar in both groups. We conclude that nucleoside transport inhibition significantly delays the breakdown of adenosine and the formation of hypoxanthine in the ischemic human myocardium.

Successful transplantation after long-term preservation of dog hearts.

Nucleoside transport inhibition is a new approach to long-term preservation of donor hearts. To evaluate its effectiveness, the following were tested: 1) the effect of nucleoside transport inhibition on high-energy phosphate content after cardioplegic arrest and during long-term cold storage (group I: cardioplegia, control ]n = 18]; group II: cardioplegia plus nucleoside transport inhibitor [n = 18]); 2) the effect of nucleoside transport inhibition on high-energy phosphates and hemodynamic recovery in a modified blood-perfused Langendorff system (group III: 24-h cold storage followed by reperfusion [n = 6]; group IV: addition of nucleoside transport inhibition to cardioplegia but not during reperfusion [n = 6]; group V: addition of nucleoside transport inhibition during reperfusion [n = 6]; group VI: addition of nucleoside transport inhibition to cardioplegia and during reperfusion [n = 6]); and 3) the effect of nucleoside transport inhibition added to cardioplegia and during reperfusion on high-energy phosphate content and outcome after heart transplantation (group VII: no nucleoside transport inhibitor in cardioplegia and during reperfusion [n = 8]; group VIII: addition of nucleoside transport inhibition to cardioplegia and during reperfusion [n = 8]). The following results were obtained: 1) addition of nucleoside transport inhibition prevented high-energy phosphate depletion during cold storage: after 24 h, adenosine triphosphate content in group I was 9.4 +/- 3.1 mumol/g versus 17.7 +/- 3.6 mumol/g dry weight in group II (P less than 0.05); 2) addition of nucleoside transport inhibition to cardioplegia and during reperfusion resulted in greater high-energy phosphate content (adenosine triphosphate in group III was 7.9 +/- 3.5 mumol/g vs. 17.8 +/- 2.8 mumol/g in group VI [P less than 0.05]) and improved hemodynamics upon reperfusion (hearts in group III did not recover, maximum isometric left ventricular pressure development was 1,635 +/- 577 mmHg/sec in group IV, 1,915 +/- 423 mmHg/sec in group V, and 2,437 +/- 201 mmHg/sec in group VI [P less than 0.05, group VI vs. groups IV and V]); and 3) hearts treated with nucleoside transport inhibition in cardioplegia and during reperfusion (group VIII) could be transplanted successfully in contrast to group VII hearts. These data indicate that nucleoside transport inhibition in dogs is highly effective in long-term preservation of donor hearts.

Degradation of myocardial high-energy phosphates during twenty-four hours of cold storage. Effects of cardioplegic versus noncardioplegic arrest.

Purine nucleotide catabolism was examined during 24 hours of cold (0.5 degree C) storage of human transplant recipient hearts, baboon hearts, and dog hearts. The hearts were excised either after cold hyperkalemic cardioplegic arrest or after simple hypothermic arrest (25 degrees C). In human myocardium, hypothermia alone preserved the adenosine triphosphate pool markedly. Even after 24 hours of cold storage, adenosine triphosphate was still 9.5 +/- 2.5 mumol/gm dry weight (58% of the preischemic value). The major fraction of catabolites remained nucleotides: adenosine triphosphate plus adenosine diphosphate plus adenosine monophosphate decreased only from 99% +/- 1% (preischemic value) to 80% +/- 13% of the total purine content. The remaining catabolites were mainly nucleosides (adenosine 0.2% +/- 0.1% and inosine 19% +/- 13% of the total purine content). Cardioplegic arrest before cold storage did not change the pattern of purine nucleotide catabolism in any respect (p greater than 0.05). In baboon myocardium, hypothermia alone preserved the adenosine triphosphate content somewhat less than in human myocardium. Adenosine triphosphate content after 24 hours was 5.2 +/- 1.6 mumol/gm dry weight (40% of the preischemic value). The catabolism of adenosine triphosphate, however, did not proceed far beyond the level of adenosine monophosphate, so that the sum of nucleotides remained the same as in human hearts. Adenosine was 0.2% +/- 0.3% and inosine 17% +/- 4% of the total sum of purines. Also in the baboon heart, cardioplegia did not influence the pattern of catabolism significantly (p greater than 0.05). In the dog myocardium, hypothermia alone did not protect against severe catabolism of adenosine triphosphate. The adenosine triphosphate content at 24 hours of storage was 3.5 +/- 2.5 mumol/g dry weight (25% of the preischemic value). Catabolism of adenosine triphosphate proceeded far beyond the level of the nucleotides (63% +/- 17% of the total sum of purines), resulting in an accumulation of adenosine and inosine (5% +/- 4% and 30% +/- 13% of the total sum of purines) and even of hypoxanthine (1% +/- 1% of the total sum of purines). In the dog heart cardioplegic arrest inhibited adenosine triphosphate catabolism considerably. Adenosine triphosphate content at 24 hours was 8.1 +/- 1.8 mumol/gm dry weight (56% of the preischemic value); 83% +/- 5% of the total purine content remained present as nucleotides, and the nucleoside content was reduced to 2% +/- 3% for adenosine and 11% +/- 6% for inosine.(ABSTRACT TRUNCATED AT 400 WORDS)

A new concept of long-term donor heart preservation: nucleoside transport inhibition.

Myocardial ischemia results in a breakdown of adenosine triphosphate (ATP), which is associated with an accumulation of its catabolites adenosine and inosine. Adenosine is a potent but ineffective cardioprotective agent because it is rapidly transported to the endothelium and irreversibly catabolized. With the use of specific nucleoside transport inhibition (NTI), however, endogenous adenosine may accumulate at its site of production, and its further breakdown and washout on reperfusion is prevented. In this study we tested this concept and assessed the effect of NTI drug administration on 24 hours' preservation of donor hearts for transplantation. Twelve dogs were randomly allocated to two groups. In the first group (group 1, n = 6) the hearts were arrested with a cold hyperkalemic cardioplegic solution, excised and stored for 24 hours at 0.5 degrees C. After 24 hours the hearts were transplanted orthotopically. In group 2 (n = 6) the same procedure was followed, but a specific NTI agent was added to the cardioplegic solution (1 mg/L) and administered intravenously to the recipient dog before reperfusion of the transplanted heart (0.1 mg/kg). Despite maximal positive inotropic support, none of the control animals (group 1) could be weaned from cardiopulmonary bypass: within 1 hour irreversible cardiogenic shock occurred in all animals. In group 2 all hearts could be weaned from cardiopulmonary bypass and were hemodynamically stable without positive inotropic support. Serial transmural left ventricular biopsies revealed in group 1 moderate catabolism of ATP during cold storage. On reperfusion a further decline of the ATP content was seen, and the accumulated nucleosides were washed out.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of hypothermic ischemia on purine catabolism in canine, primate, and human myocardium.

After hypothermic cardiac arrest, creatine phosphate (CrP) and adenine nucleotide catabolism was compared in myocardium from dogs (n = 7), baboons (n = 5), and man (n = 7; patients undergoing cardiac transplantation) during cold (0.5 degree C) storage for up to 24 hours. Although hypothermia delayed the catabolism in dog myocardium it still remained very extensive. CrP dropped to virtually nil and ATP fell to below 15% of the total purines within 6 hours. The majority of the adenine nucleotides was broken down to adenosine (ADO; 32% of total purines) and inosine (INO; 21%). Apart from the delay (7 to 9-fold), hypothermia also reversed the ratio between ADO and INO when compared to normothermia, suggesting a profound effect of temperature on the nucleoside transporter. In human myocardium even after 12 hours of hypothermia ATP still contributed more than 60% to the total purines. Concomitantly, nucleoside formation proceeded slowly with almost no intermediate ADO. Under similar conditions, the catabolism of ATP in baboon myocardium occurred at a higher rate than in man but still far below canine metabolism. Irrespective of the relatively higher fall in ATP, ADP and AMP accumulated more in baboon myocardium indicating a limited dephosphorylation of the nucleotides. Only in the baboon myocardium did inosine monophosphate increase above the detection limits. In none of the species did purine catabolism proceed beyond hypoxanthine and even this could hardly be detected in the primates. It is concluded that considerable species differences do exist in the rate as well as in the pattern of nucleotide catabolism even during storage of the myocardium at low temperature.

Catabolism of high energy phosphates during long-term cold storage of donor hearts: effects of extra- and intracellular fluid-type cardioplegic solutions and calcium channel blockers.

Dog hearts were harvested and stored cold (0.5 degree C) for 24-hours. Cardiac arrest was induced by means of low-sodium and calcium-free cardioplegic (n = 6) or hyperkalemic cardioplegic (n = 6) solution. Nifedipine (2 micrograms/gm estimated heart weight) was added to each cardioplegic solution in two additional groups (n = 6 each). High energy phosphates (creatine phosphate and adenosine triphosphate) and catabolites (adenosine diphosphate and monophosphate, adenosine, inosine, hypoxanthine, xanthine) were determined in the myocardium before and during 24 hours of cold storage. With use of the standard hyperkalemic cardioplegic solution, breakdown of high energy phosphates was less pronounced than after the use of a low sodium, calcium-free solution: after 24 hours of cold storage myocardial ATP content was 57% of control versus 32% (p less than 0.05). The addition of nifedipine to the hyperkalemic cardioplegic solution delayed ATP breakdown during the first hours of cold storage: at 5 hours of preservation the myocardial ATP level was significantly higher (p less than 0.05) than in hearts preserved without nifedipine. Addition of nifedipine to the low-sodium, calcium-free solution did not influence catabolism of high energy phosphates significantly. It is concluded that preservation of high energy phosphates during long-term cold storage of donor hearts can be best achieved by simultaneous myocardial metabolic blockade at two specific sites: at the "fast" sodium-potassium channels by hyperkalemic depolarization and at the "slow" channels by means of calcium channel blockers.

[Catabolism of high-energy phosphates during the long-term preservation of explanted donor hearts in a dog model]. / Katabolismus energiereicher Phosphate während der Langzeitpräservierung explantierter Donor-Herzen im Hundemodell.

The catabolism of high-energy phosphates (HEP) during long-term preservation of donor hearts was investigated in mongrel dogs. Hearts were explanted after being randomly assigned to one of the following groups. Group I: normothermic ischaemic arrest (n = 6), group II: hypothermic ischaemic arrest (n = 6), group III: cardioplegic arrest with NIH cardioplegia (n = 6) and group IV: cardioplegic arrest with UW solution (n = 6). After explantation all hearts were stored cold for 24 hours, achieving a myocardial temperature of 0,5 degrees C. HEP content (ATP and creatine phosphate) and catabolites were determined from serial left ventricular biopsies taken before explantation and during cold storage. A significant decrease of HEP content was found in all groups. In group I and II a significant decrease of HEP was found after one hour of cold storage. After 4 and 8 hours cold storage ATP content was significantly higher in group II. Cardioplegic arrest of dog hearts resulted in a significantly delay of HEP depletion. In group III a significant decrease of ATP was only seen after 12 hours and in group IV already after 6 hours of cold storage. Hearts preserved with the newly developed UW solution showed significantly lower ATP values after 10, 12 and 24 hours than NIH preserved hearts. It is concluded that UW solution is less advantageous than NIH solution in terms of HEP preservation.

Long-term preservation of baboon hearts. Effects of hypothermic ischemic and cardioplegic arrest on high-energy phosphate content.

Baboon hearts were preserved ex vivo after hypothermic ischemic or cardioplegic arrest and were stored cold (0.5 degrees C) for 24 hours. Ischemic arrest was induced on cardiopulmonary bypass after general cooling to 25 degrees C. Cardioplegic arrest was induced using either a hyperkalemic standard cardioplegic solution National Institutes of Health [( NIH] solution) or the recently developed University of Wisconsin (UW) organ preservation solution. ATP and catabolites were assessed in serial transmural biopsies. Cardioplegia significantly delayed the breakdown of ATP during storage. After infusion of the adenosine-supplemented UW solution, myocardial content of adenosine was high as compared with that in NIH-arrested hearts (9.12 versus 0.01 mumol.g-1 dry wt). During cold storage, however, adenosine converted to inosine in spite of profound hypothermia. This renders unlikely the potential of fast resynthesis of ATP out of the supplemented nucleoside pool after reoxygenation.

Effects of left ventricular assist for cardiogenic shock on cardiac function and organ blood flow distribution.

Organ blood flow distribution was studied in dogs subjected to a left ventricular assist device (LVAD). In normal hearts (group 1), left ventricular work was reduced by 25% when 35% of cardiac output was performed by the LVAD. Organ perfusion, measured with tracer microspheres, remained normal or slightly increased. After induction of cardiogenic shock (group 2), perfusion deteriorated in all organs, but first in the brain, kidney, and intestinum. All animals died within 1 hour. When maximal inotropic support was administered after shock (group 3), hemodynamics improved but perfusion to most organs decreased progressively and 83% of animals died within 2 hours. When the LVAD was inserted after shock but without inotropic support (group 4), perfusion of all organs became normal during LVAD except for kidney flow, which remained severely depressed (56% of preshock value). After LVAD insertion, hemodynamics did not recover completely, and 33% of the animals died within 3 hours. When use of the LVAD was combined with 5 micrograms.kg-1.min-1 of dopamine after shock (group 5), organ blood flow distribution became normal during and after LVAD use except for renal flow, which was significantly impaired (83% of preshock value). Hemodynamics recovered after LVAD use, and all animals survived in this group. We conclude that use of the LVAD combined with low-dose positive inotropic support can prevent deterioration of organ perfusion after cardiogenic shock except for kidney.

Reperfusion injury after 24 hours cold storage of donor hearts. Possible role of leukocyte activation.

The role of neutrophils on the development of reperfusion injury was evaluated in canine hearts. Reperfusion was performed with a closed reperfusion system. 18 dog hearts were arrested by a single dose of National Institute of Health cardioplegia and stored cold (0.5 degrees C) for 24 hours. Thereafter they were randomly attached to one of the following groups. Group I: reperfusion with whole blood (n = 6), group II: reperfusion with low-leukocyte blood (n = 6), group III: reperfusion with low-leukocyte blood plus phenyl-isopropyl adenosine (PIA) (n = 6). Hearts in group I showed an increase of high energy phosphates (HEP) within the first 30 minutes, and a significant decrease during the subsequent 30 minutes. Concomitantly the initially soft hearts turned into stone hearts. In group II and III a significant increase of HEP was seen during the entire reperfusion. After 60 minutes of reperfusion myocardial ATP levels in group III were significantly higher than in group I. All hearts in group III were soft after reperfusion. It is concluded that reperfusion injury appears to be dependent upon the presence and activation of neutrophils, which can be partially prevented by reperfusion with low-leukocyte blood and more so by the simultaneous administration of PIA.

[Two cases of malignant cardiac tumors attached on the anterior mitral valve].

Two cases were reported in which malignant cardiac tumors attached to the mitral valve were diagnosed during their lifetimes using two-dimensional echocardiography. Case 1 was a 29-year-old man with speech disturbance and left hemiparesis. Histological examination of the specimen excised from the cardiac tumor during the operation revealed mesenchymal chondrosarcoma, which is extremely rare etiologically and has never been reported so far. Case 2 was a 62-year-old woman complaining of paroxysmal nocturnal dyspnea and chest pain. The diagnosis of malignant histiocytosis was made from the pathological examination of biopsy specimen taken from the rib metastasis. Using two-dimensional echocardiography, characteristic findings for the cardiac tumor were obtained. The tumor echo in Case 1 showed, unlike to that reported for myxoma, two different echogenic layers; the outer dense and the inner light in the echo density. On surgery, tumor echo was revealed to reflect the cystic lesion. In Case 2, two-dimensional echocardiography on admission revealed two separate tumor echoes which attached to the mitral valve and left atrial wall region, respectively. Within two months, they grew rapidly and finally fused into one mass resulting in so-called ball valve syndrome. Phonocardiographically, the tumor plop in Case 1 was high-pitched in quality, and was extinguished completely after the tumor was resected. The tumor plop in Case 2 was not audible on admission, but became evident after fusion of the tumor echoes and was associated with a presystolic murmur.