Two-Step Operation for Aortoesophageal Fistula After Thoracic Endovascular Repair.

Aortoesophageal fistula (AEF) caused after thoracic endovascular aortic repair (TEVAR) is rare but a serious complication. We report a successful staged operation for AEF after TEVAR. A 70-year-old male underwent TEVAR for a ruptured aneurysm of the descending aorta and subsequently developed AEF three months later. First, the patient underwent the resection of the esophagus, which was the focus of the infection under the right thoracoscopic approach. Second, descending aorta replacement was performed using a left thoracotomy approach. The patient has been well for about two years since the second operation without recurring graft infection. Staged operation with a different approach to the infection zone is a useful method for AEF.

Impact of Recovery from Acute Kidney Injury After Aortic Arch Repair.

BACKGROUND: The impact of recovery from acute kidney injury (AKI) after open thoracic aortic surgery on follow-up outcomes is unclear. METHODS: This retrospective study included 214 patients who underwent aortic arch surgery requiring hypothermic circulatory arrest between 2007 and 2019. Patients who required preoperative renal replacement therapy and patients who died within 7 postoperative days were excluded. The incidence of recovery from AKI was examined. Renal outcomes were compared among patients with no AKI (Group N), recovery from AKI (Group R), and persistent AKI (Group P). RESULTS: Preoperative kidney function was similar among the 3 groups. Among the 115 patients who developed postoperative AKI, 80.9% recovered from AKI at discharge. The 5-year cumulative mortality rate was 18.0%, 24.5%, and 68.4% in Group N, R, and P, respectively (P < .001, Group R vs Group P). The 5-year cumulative incidence of renal replacement therapy dependency was 0.0%, 5.4%, and 22.7%, respectively (P = .04, Group N vs Group R; P = .01, Group R vs Group P). The medians (interquartile range) of estimated glomerular filtration rate (mL/min/1.73 m2) 2 years after surgery were 65.2 (50.4-80.2), 54.3 (41.4-65.9), and 56.9 (40.2-67.5), respectively (P = .03, Group N vs Group R). CONCLUSIONS: The majority of patients recovered from AKI after thoracic aortic repair by discharge. However, the prolonged impact of AKI recovery on kidney function was observed during the follow-up period. Diligent follow-up after discharge is warranted for early identification of patients at high risk of kidney disease progression.

Thrombocytopenia recovered by surgical resection of a myxoma.

Myxoma is the most common primary cardiac neoplasm, and causes a variety of symptoms, including hematological disorder. An 82-year-old man with anorexia was diagnosed with a gastrointestinal stromal tumor. Computed tomography and echocardiography showed a 2-cm tumor in the left atrium. The patient had a history of lung and skin sarcoidosis, and interstitial pneumonia. Laboratory examination showed thrombocytopenia with a platelet count of 23 × 103/µL and elevation of IgA and platelet-associated IgG (PAIgG). We suspected that the thrombocytopenia was caused by the left atrial tumor. He successfully underwent resection of the tumor with cardiopulmonary bypass. The platelet count increased to 166 × 103/µL after surgery. Pathological examination showed Alcian blue staining of the extracellular and intracellular matrix, suggesting a mucopolysaccharide matrix. Immunohistochemical examination of the tumor revealed expression of CD31, CD34, and calretinin, which was consistent with a myxoma. The PAIgG level decreased to the normal range at 36 days postoperatively. Thrombocytopenia is a relatively rare finding in patients with myxomas. However, in addition to mobility of the mass, thrombocytopenia should be kept in mind as an indication for surgery. .

Surgical repair of unroofed coronary sinus with severe mitral regurgitation in an elderly patient.

An unroofed coronary sinus (URCS) is a rare anomaly that produces communication between the left atrium (LA) and the coronary sinus (CS), resulting in a left-to-right shunt. Due to the lack of symptoms and particular anatomical characteristics, this disease is difficult to diagnose, and prone to be overlooked. An 85-year-old man was admitted to our hospital because of anorexia and shortness of breath. On physical examination, a systolic murmur was heard at the apex, and pitting edema was present in both legs. Transthoracic echocardiography showed severe regurgitation of the mitral valve and tricuspid valve. Transesophageal echocardiography confirmed a shunt between the LA and the CS. Because of uncontrolled heart failure, we performed surgical repair 50 days after admission. Under cardiopulmonary bypass and heart arrest, the URCS was detected in the LA and directly sutured. Repair of the mitral and tricuspid valves and the Maze procedure were also performed. The patient had a good postoperative course, and has been doing well for 2 years. Transesophageal echocardiography is helpful for diagnosis of URCS. Mitral regurgitation might raise the left atrial pressure and result in increase in shunt flow, causing left and right heart failure in elderly patients. .

Flat fibrin thrombus deposition on tissue valve after aortic valve replacement.

Bioprosthetic valves have a lower thrombogenicity than mechanical valves, thus long-term systemic anticoagulation can be avoided. Herein, we present an extremely rare case of fibrin thrombus formation on tissue valve, which was observed during the second operation 2 years after the initial operation by chance. This report gives us a word of caution regarding the thrombus formation on the bioprosthetic valves that could be unaware of the presence for the long term.

Delivery route in bone marrow cell transplantation should be optimized according to the etiology of heart disease.

BACKGROUND: Recent studies have revealed that bone marrow cell (BMC) transplantation is effective not only for myocardial infarction (MI), but also for dilated cardiomyopathy (DCM). However, the method of administering donor cells remains unknown, and may differ between MI and DCM. In the present study, intramyocardial (IM) injection and intravenous (IV) delivery of BMC were compared in each etiological model. METHODS AND RESULTS: MI was induced in 72 mice and DCM in another 36 mice by doxorubicin. BMCs were administered IV or IM in an acute MI (AMI), old MI (OMI) or DCM model. In the AMI model, left ventricular (LV) remodeling was reduced in both the IM- and IV-groups, but only in the IM-group in the OMI model. In the DCM model, the LV dimension of the IV-group was smaller than that of the IM-group. Histological examination showed that green fluorescent protein (GFP) cells were equally distributed in the infarct area of the IV- and IM-groups in AMI, and in the IM-group in the OMI model. In the DCM model, GFP cells were diffusely scattered throughout the ventricular wall in the IV-group, but were confined to the injection site in the IM-group. CONCLUSIONS: In OMI, IM delivery of BMCs was more effective than IV; however, IV delivery was superior in DCM. Delivery route should be selected according to the etiology of heart disease to optimize the efficacy of BMC transplantation.

Fracture embolization of an Edwards-Duromedics valve with asymmetrical closure.

We report a case of sudden leaflet fracture of an Edwards-Duromedics mitral valve 17-years after its implantation. The patient had a history of an asymmetrical motion of the valve, five months earlier. A computed tomography scan showed two fragments that had embolized to the right brachiocephalic artery and left common iliac artery. An emergency mitral replacement surgery was successfully performed. Asymmetrical closure of the valve leaflet may have contributed to valve fracture.

Attenuating effects of chymase inhibitor on pericardial adhesion following cardiac surgery.

OBJECTIVE: Chymase, a serine protease, is released from mast cells, which is closely associated with adhesion formation. Chymase activates transforming growth factor-beta1 (TGF-beta1), which promotes tissue fibrosis. Recently we have found that chymase may play an important role in adhesion formation in hamsters. Accordingly, this study was designed to confirm that a chymase inhibitor prevents postoperative cardiac adhesions in large animals. METHODS: In 14 dogs, the epicardium was abraded 200 times with gauze and the mid-portion of the left anterior descending coronary artery (LAD) was exposed with No. 15 blade. Either chymase inhibitor (CI group, n = 7) or placebo (P group, n = 7) was sprayed into the pericardial cavity, then the pericardium was closed. Cardiac chymase activity, the level of TGF-beta1 in the pericardial fluid, the density of epicardial mast cells, the adhesion area between the heart and the pericardium, and the presence of adhesion between the mid-LAD and the pericardium were evaluated 1 and 2 months after surgery. Five nonsurgical dogs were used as a control for cardiac chymase activity. RESULTS: Cardiac chymase activity and TGF-beta1 level were lower in CI group than in P group (53.7 +/- 35.0 vs. 93.4 +/- 20.4 microU/mg protein, p = 0.01, 3.2 +/- 0.9 vs. 4.3 +/- 1.1 microg/mL, p = 0.06, respectively). In CI group, the density of mast cells (19 +/- 5 vs. 32 +/- 8 cells/cm, p < 0.01), the adhesion area (2.2 +/- 0.8 vs. 7.5 +/- 1.5 cm2, p < 0.01), and adhesions between the heart and the mid-LAD (0% vs. 57%) were all reduced. CONCLUSION: Chymase inhibitor suppresses cardiac chymase activity and reduces the TGF-beta1 level, resulting in a reduction of cardiac adhesion in a large animal.

Mitral annuloplasty as a ventricular restoration method for the failing left ventricle: a pilot study.

BACKGROUND AND AIM OF THE STUDY: Undersized mitral annuloplasty (MAP) is effective in patients with dilated cardiomyopathy and functional mitral regurgitation (MR) since, as well as addressing the MR, the MAP may also reshape the dilated left ventricular (LV) base. However, the direct benefits of this possible reshaping on LV function in the absence of underlying MR remain incompletely understood. The study aim was to identify these benefits in a canine model of acute heart failure. METHODS: Six dogs underwent MAP with a prosthetic band on the posterior mitral annulus, using four mattress sutures. The sutures were passed individually through four tourniquets and exteriorized untied via the left atriotomy. Sonomicrometry crystals were implanted around the mitral annulus and left ventricle to measure geometry and regional function. Acute heart failure was induced by propranolol and volume loading after weaning from cardiopulmonary bypass; an absence of MR was confirmed by echocardiography. MAP was accomplished by cinching the tourniquets. Data were acquired at baseline, after induction of acute heart failure, and after MAP. RESULTS: MAP decreased mitral annular dimensions in both commissure-commissure and septal-lateral directions. Concomitantly, the diastolic diameter of the LV base and LV sphericity decreased (i.e., improved) from 37.4 +/- 9.3 to 35.9 +/- 10 mm (p = 0.063), and from 67.9 +/- 18.6% to 65.3 +/- 18.9% (p = 0.016), respectively. Decreases were evident in both LV end-diastolic pressure (from 17 +/- 7 to 15 +/- 6 mmHg, p = 0.0480 and Tau (from 48 +/- 8 to 45 +/- 8 ms, p <0.01), while fractional shortening at the LV base increased from 7.7 +/- 4.5% to 9.4 +/- 4.5% (p = 0.045). After MAP, increases were identified in both cardiac output (from 1.54 +/- 0.57 to 1.65 +/- 0.57 1/min) and Emax (from 1.86 +/- 0.9 to 2.41 +/- 1.31 mmHg/ml). CONCLUSION: The data acquired suggest that isolated MAP may have certain benefits on LV dimension/function in acute heart failure, even in the absence of MR. However, further investigations are warranted in a model of chronic heart failure.

Enhanced angiogenesis by gelatin hydrogels incorporating basic fibroblast growth factor in rabbit model of hind limb ischemia.

Recently we have developed new sustained release system of basic fibroblast growth factor (bFGF) using gelatin hydrogel as a carrier. Using this system, we examined the effect of topical sustained release of bFGF on angiogenesis and tissue blood perfusion in a rabbit model of hind limb ischemia. Thirty-two rabbits underwent excision of right femoral artery under general anesthesia. Two weeks later the rabbits were randomized into four groups (n = 8 each): no treatment, intramuscular injection of gelatin hydrogel alone, and intramuscular injection of gelatin hydrogel incorporating 30 microg and 100 microg of bFGF. Four weeks after each treatment, selective angiography, tissue blood flowmetry using laser Doppler perfusion imaging, and histological examination of thigh muscle were performed. In groups treated with bFGF incorporating gelatin hydrogel, tissue blood flow, number of arterioles, and vascular density were significantly increased in a dose-dependent manner 4 weeks after the treatment. Serum concentrations of bFGF and vascular endothelial growth factor were not elevated 4 weeks after the treatment. In conclusion, sustained release of bFGF using gelatin hydrogel augmented angiogenesis and improved tissue blood flow after excision of the femoral artery.

Human gastroepiploic artery has greater chymase activity than the internal thoracic artery.

OBJECTIVE: Recent reports have demonstrated that long-term patency of the gastroepiploic artery (GEA) in coronary artery bypass grafting (CABG) is less satisfactory compared with the internal thoracic artery (ITA). However, the reason has not been fully elucidated. Angiotensin II is known to play an important role in the development of intimal hyperplasia, we hypothesized that the GEA is different from the ITA with respect to angiotensin II-forming ability. Accordingly, we measured activities of angiotensin II-forming enzymes, angiotensin-converting enzyme (ACE) and chymase, in human GEA and ITA. METHODS: Remnant of the GEAs and ITAs were obtained from 24 patients who underwent CABG in which both conduits were used simultaneously. Activities of ACE and chymase were measured by using the extract form the GEA or ITA. Sections of the GEA or ITA were immunohistochemically stained with anti-human chymase antibody. RESULTS: The ACE activity of the GEA (0.28+/-0.16 mU/mg protein) was greater than that of the ITA (0.18+/-0.11, p < 0.001). The chymase activity of the GEA (11.11+/-7.15 mU/mg protein) was also greater than that in the ITA (7.13+/-4.89, p < 0.001). The density of chymase-positive cells in the GEA (3.8+/-4.2 cells/mm2) was greater than that in the ITA (1.1+/-1.2, p < 0.01). CONCLUSION: Activities of both ACE and chymase were significantly greater in the GEA compared with the ITA. The GEA may be different from the ITA with respect to potential ability of angiotensin II-formation.

Comparison of efficacy of medium-sized cutting balloons versus standard balloons for dilation of peripheral pulmonary stenosis.

The efficacy of medium-sized cutting balloons (CBs) 5 to 8 mm in diameter was compared with that of standard balloons (SBs) in the dilation of peripheral pulmonary stenosis (PPS). Nine vascular lesions in 7 patients were primarily dilated by CBs, and 13 vascular lesions in 11 patients were dilated by SBs alone. The efficacy of balloon dilation was evaluated by angiography and intravascular ultrasound (IVUS). There was no significant difference between the 2 groups in the success rate (66% vs 62%), the percentage increase in minimal lesion diameter (MLD; median 71% vs 52%) on angiography, and the number of new tears (2 vs 1) on IVUS. However, in the subgroup of vascular lesions with MLDs of <4.0 mm, for which CBs with diameters >200% of the MLD could have been applied, the percentage increase in MLD (95% vs 53%, p <0.05) and the number of tears (2 vs 1, p <0.05) with CBs were significantly greater than with SBs, requiring significantly smaller maximum balloon pressure (10 vs 13 atm, p <0.05). CBs are as effective as conventional balloons in the dilation of PPS and may be more effective when larger balloons are available.

Control-released hepatocyte growth factor prevents the progression of heart failure in stroke-prone spontaneously hypertensive rats.

BACKGROUND: We have developed a hepatocyte growth factor (HGF)-incorporating gelatin hydrogel sheet (HGF sheet), which was designed to release HGF more than 2 weeks in vivo. The present study investigated whether the HGF sheet could prevent the progression of heart failure in stroke-prone spontaneously hypertensive rats. METHODS: Stroke-prone spontaneously hypertensive rats at the age of 25 weeks received placement of an HGF sheet on the left ventricular free wall (HGF, n = 10) or sham-operation (control, n = 10). All animals were followed up with Doppler echocardiography during the next 4 weeks and then underwent histologic analysis. The influence of the hydrogel sheet alone was assessed by echocardiography and left ventricular pressure measurements. Survival study was performed (each group, n = 11) at the age of 30 weeks. RESULTS: There were two deaths in the control group and no deaths in the HGF group during the 4 weeks. Fractional shortening was significantly higher, and left ventricular diastolic dimension was significantly smaller in the HGF than in the control group. The slope of the peak early diastolic filling velocity and the ratio of that slope to the slope of the peak filling velocity at atrial contraction were significantly lower in the HGF than the control group. Myocardial fibrosis was lower and capillary density was significantly higher in the HGF than the control group. Placement of the hydrogel sheet alone did not affect any cardiac function compared with sham operation. The survival rate at 10 weeks after the surgery was much higher in the HGF than the control group. CONCLUSIONS: The HGF sheet improves cardiac function, reverses left ventricular remodeling, and markedly improves survival in spontaneously hypertensive rats. These beneficial effects are associated with angiogenesis and reduced fibrosis in the left ventricular myocardium.

Heterotopic transplantation of the failing rat heart as a model of left ventricular mechanical unloading toward recovery.

The left ventricular assist device (LVAD) is usually used in patients with end-stage heart failure as a bridge to transplantation. Recently, some studies have reported functional recovery with the use of an LVAD, although the mechanisms responsible for recovery are not fully understood. We investigated the functional recovery of the infarcted, failing rat heart in response to mechanical unloading after heterotopic transplantation. Heart failure was induced in Lewis rats by ligating the left anterior descending artery. After 4 weeks, the infarcted hearts were harvested and heterotopically transplanted. The transplanted infarcted heart was removed after 2 weeks of unloading and examined for hypertrophy and fibrosis, as well as for mRNA levels encoding for brain natriuretic peptide, sarco(endo)plasmic reticulum Ca(2+)-ATPase2a (SERCA2a), and beta1- and beta2-adrenergic receptors. Normal and infarcted rats without transplantation served as control animals. The infarcted heart was hypertrophied as evidenced by an increase in heart weight and myocyte diameter. After unloading the infarcted heart for 2 weeks, there was a decrease in heart weight and myocyte diameter. However, the percentage of myocardial fibrosis increased after unloading. The mRNA expression of brain natriuretic peptide and the beta2-adrenergic receptor significantly improved after mechanical unloading. The levels of SERCA2a mRNA tended to increase after unloading. In conclusion, unloading the failing, infarcted heart can help normalize left ventricular hypertrophy and cardiac gene expression. This unloading model appears to partially mimic the conditions of hemodynamic support with an LVAD in heart failure patients and potentially offers insights into the mechanisms of functional recovery.

Maintenance of pulmonary vasculature tone by blood derived from the inferior vena cava in a rabbit model of cavopulmonary shunt.

INTRODUCTION: After cavopulmonary shunt in which the superior vena cava is anastomosed to the right pulmonary artery, the right lung is in a unique condition without flow pulsatility and hepatic venous effluent. In a previous study, we reported that hypoxic pulmonary vasoconstriction disappeared in the pulmonary circulation after cavopulmonary shunt. In this study, however, to investigate the influence of pulsatility and hepatic venous effluent on hypoxic pulmonary vasoconstriction in the pulmonary circulation, we developed an alternative cavopulmonary shunt rabbit model that included hepatic venous effluent in the pulmonary circulation and reduced the pulsatility of the pulmonary arterial blood flow. We then observed the physiologic characteristics of the peripheral pulmonary artery after cavopulmonary shunt, specifically the disappearance of hypoxic pulmonary vasoconstriction. METHODS: Sixteen Japanese white rabbits (12-16 weeks old) were used in this study. With general anesthesia, a cavopulmonary shunt was established by anastomosing the right superior vena cava to the right pulmonary artery in an end-to-side fashion. Of the 16 rabbits for the study, the proximal right pulmonary artery was completely ligated in 5 (atresia group) and partially ligated in 6 (stenosis group). Sham operation was performed in the remaining 5 rabbits. Two weeks later, we analyzed the response of the pulmonary artery (which was divided into three categories: segmental, lobular, and acinar level artery) to hypoxia (8% oxygen inhalation) with a specially designed video radiographic system. Morphometric analysis of the resistance pulmonary artery was done in each group after angiography. RESULTS: Mean pressure and pulse pressure in the right pulmonary artery were not significantly different between the atresia and stenosis groups. The mean pulmonary artery pressures in the atresia and stenosis groups were 8 and 11 mm Hg, respectively. However, the pulse pressure was less than 2 mm Hg in both groups. The baseline internal diameter of the resistance pulmonary artery of the atresia group was significantly different from those of the stenosis and sham groups. In the atresia group, the resistance pulmonary arteries did not respond to hypoxia. In contrast, significant constriction (as assessed by percentage change of internal diameter of the resistance pulmonary arteries in the acinar and lobular level arteries) was observed in the pulmonary arteries of the sham and stenosis groups (atresia vs stenosis vs sham 0.4% vs - 19.0% vs - 18.8%, P = .01). In our morphometric study, we observed vasodilation of the resistance pulmonary artery with a thinner medial layer in the atresia group, consistent with the result of microangiography. CONCLUSION: We developed a cavopulmonary shunt rabbit model in which the inferior vena caval blood was derived from the right ventricle. Hypoxic pulmonary vasoconstriction was maintained in the model with the blood flow from the right ventricle. When the blood flow was not maintained, however, hypoxic pulmonary vasoconstriction disappeared. This phenomenon strongly suggests that a substance in hepatic venous effluent partially regulates the physiological pulmonary vascular function in the rabbit lung.

Residual fibrosis affects a long-term result of left ventricular volume reduction surgery for dilated cardiomyopathy in a rat experimental study.

OBJECTIVES: The aim of this study is to evaluate the relationship between left ventricular (LV) wall property and the results of LV volume reduction surgery (LVR) to treat dilated cardiomyopathy (DCM) in an experimental model. METHODS: DCM was introduced in 18 Lewis rats by autoimmunization with cardiac myosin. Among them, 12 rats underwent LVR and the rest were served as controls. They were subjected to echocardiography and cardiac catheterization for dimensional and functional measurements. The animals were sacrificed 4 weeks after surgery, and the fraction of myocardial fibrosis was calculated in 4 divided parts of the LV wall. RESULTS: Percent fibrosis varied widely from 4.7 to 45.2%. LV volume reduction surgery improved cardiac function immediately after surgery in all rats (Emax, 0.28+/-0.14 to 0.48+/-0.18 mmHg/microl; LV end-diastolic pressure, 21.0+/-6.1 to 13.3+/-5.1 mmHg, P<0.05, respectively). Four weeks later, 6 hearts remained in good shape with smaller LV end-diastolic dimension (Dd) than baseline values (LV Dd, 9.7+/-0.6mm; fractional area change (FAC), 40.3+/-8.4%) and the other 6 had more redilation in diameter and more deterioration in function than baseline values (LV Dd, 10.9+/-0.6mm; FAC, 25.8+/-6.9%; P<0.05, respectively). Percent fibrosis in the septum differed 11.1+/-3.4 vs. 27.8+/-2.8% between the two groups (P<0.01). There was a significant correlation between the ratio of LV redilatation after surgery and percent fibrosis in the septum (r=0.951, P<0.01). CONCLUSIONS: Although the initial benefit of LVR was confirmed, the long-term result was affected by the amount of residual fibrosis. This information suggests that surgical site selection is important to achieve a good result of LV restoration surgery for DCM.

Atrial natriuretic peptide helps prevent late remodeling after left ventricular aneurysm repair.

BACKGROUND: Left ventricular aneurysm repair (LVR) reduces LV wall stress and improves LV function. However, as we reported previously, the initial improvement of LVR was short-term because of LV remodeling but could be maintained longer with postoperative use of an angiotensin-converting enzyme (ACE) inhibitor. Atrial natriuretic peptide (ANP) has been used to treat patients with heart failure by natriuretic and vasodilatory actions. Recent reports have suggested that ANP inhibits the rennin-angiotensin system. In this study, the effects of ANP after LVR were evaluated. METHODS AND RESULTS: Rats that had an LV aneurysm 4 weeks after left anterior descending artery ligation underwent LVR by plicating the LV aneurysm and were randomized into 2 groups: LVR+A group was intravenously administrated with 10 microg/h of carperitide, recombinant alpha-hANP, by osmotic-pump for 4 weeks, and the LVR group was given normal saline. Echocardiography revealed better LV remodeling and function in LVR+A group than in LVR group. Four weeks after LVR, left ventricular end diastolic pressure (LVEDP) and Tau were significantly lower in LVR+A group (LVEDP: 10+/-4 in LVR+A group versus 18+/-6 mm Hg in LVR group, Tau: 13+/-2 versus 17+/-2ms). End-systolic elastance (Ees) was higher in LVR+A group (Ees: 0.34+/-0.2 versus 0.19+/-0.11 mm Hg/microL). The levels of myocardial ACE activity in LVR+A group was significantly lower than in LVR group. The mRNA expressions of brain natriuretic peptide and transforming growth factor beta1 inducing fibrosis significantly decreased in LV myocardium in LVR+A group. Histologically, myocardial fibrosis was significantly reduced in LVR+A group. CONCLUSIONS: Intravenous administration of ANP had beneficial effects on LV remodeling, function, and fibrosis after LVR. ANP could be a useful intravenous infusion drug for postoperative management after LV repair surgery.

Prevention of myocardial reperfusion injury by poly(ADP-ribose) synthetase inhibitor, 3-aminobenzamide, in cardioplegic solution: in vitro study of isolated rat heart model.

OBJECTIVE: Cardioplegic arrest remains the method of choice for myocardial protection in cardiac surgery. Poly(adenosine 5'-diphosphate-ribose) synthetase (PARS) inhibitor has been suggested to attenuate the ischemia-reperfusion injury in myocardial infarction by preventing energy depletion associated with oxidative stress. We investigated the efficacy of a cardioplegic solution containing a PARS inhibitor, 3-aminobenzamide (3-AB), for myocardial protection against ischemia-reperfusion injury caused by cardioplegic arrest. METHODS: Isolated hearts were set on a Langendorff apparatus and perfused. The hearts were arrested for 90 min with a cardioplegic solution given at 30-min intervals and then reperfused for 20 min. The hearts of rat in the 3-AB(-) group (n = 8) were perfused with a standard cardioplegic solution and terminal warm cardoplegia, whereas the 3-AB(+) group (n = 8) received these solutions supplemented with 3-AB (100 microM). Left ventricular function and release of cardiac enzymes were monitored before and after cardioplegic arrest. After reperfusion, NAD+ (nicotinamide-adenine dinucleotide) levels were assessed, and the tissues were examined immunohistochemically for oxidative stress and apoptosis. RESULTS: During reperfusion, the 3-AB(+) group showed significantly higher (P = 0.005)dp/dt and lower creatine phosphokinase (CPK) level and glucotamic-oxaloacetic transaminase (GOT) in the effluent (CPK; P = 0.003 GOT; P < 0.001) The cardiomyocytes of the 3-AB(+) group also preserved a higher NAD+ level (P < 0.001). Immunohistochemical study of oxidative stress revealed a lesser extent (P = 0.007) of nuclear staining and a lower fraction of apoptosis in the 3-AB(+) group. CONCLUSION: Cardioplegic solution supplemented with 3-AB provides efficient myocardial protection in cardioplegic ischemic reperfusion by suppressing oxidative stress and overactivation of PARS.

Pharmacological assessment of composite arterial conduits using angiography early in the postoperative period.

OBJECTIVES: Muscular arteries are vulnerable to vasospasm unlike elastic arteries. Having developed experimental models of composite arterial grafts, we assessed and compared the responses of the grafts with different pharmacological agents using angiography early in the postoperative period. SUBJECTS AND METHODS: We harvested the internal thoracic artery (ITA) and brachial-median artery (BMA) from 10 sheep. BMA was used as an alternative to the radial artery. Each vessel was assessed histologically and morphologically. Then, a serial composite graft was constructed so that BMA was interposed. On postoperative day one or two, angiography was performed on the composite graft to measure the diameter of each vessel in response to phenylephrine (alpha-adrenergic receptor agonist), nitroglycerin+phenylephrine, and milrinone+phenylephrine. RESULTS: The BMA had a wide media layer which consisted of abundant smooth muscle cells. The combined intima and media were thicker in BMA than in ITA (p<0.01). After injection of phenylephrine, the BMA diameter decreased (2.5+/-0.4 mm to 1.9+/-0.3 mm, p<0.01), while the ITA diameter remained unchanged (3.7+/-0.2 mm to 3.6+/-0.2 mm). Continuous infusion of nitroglycerin or milrinone prevented phenylephrine-induced vasoconstriction of the BMA (p<0.05). CONCLUSIONS: These results suggest that muscular arteries have a more pronounced vasoconstrictive response to alpha-adrenergic receptor agonists than the elastic arteries. To avoid potential decrease in graft flow of muscular artery, it is advisable to use a vasodilator nitroglycerin or milrinone early in the postoperative period.

Development of biologic coronary artery bypass grafting in a rabbit model: revival of a classic concept with modern biotechnology.

OBJECTIVE: We have developed a technique for biologic coronary artery bypass grafting, which is a revival of a classic concept with modern biotechnology. METHODS: Acute myocardial infarction was created by ligating the major branch of the circumflex artery in rabbits. Animals were divided into four groups: a nontreated group (group N), a group in which omentum was used to wrap the infarcted area (group G), a group in which a gelatin hydrogel sheet incorporating 100 microg basic fibroblast growth factor was placed over the infarcted area (group F), and a group in which the infarcted area was similarly treated with basic fibroblast growth factor followed by omental wrapping (group FG). Cardiac function was subsequently assessed by echocardiography. Postmortem angiography through the gastroepiploic artery was done in groups G and FG. Infarct size and arteriolar density were evaluated. RESULTS: Group FG showed a better fractional area change than did the other groups (group N P <.001, group G P =.002, group F P <.001). Angiography revealed that communication from the gastroepiploic artery to the coronary artery was created through a rich bed of neovascularization in all 7 animals of group FG, whereas poor collaterals were recognized in only 2 of 7 animals in group G. Infarct size was reduced to a greater extent in group FG than in groups F, G, and N (10% +/- 3%, 16% +/- 5%, 19% +/- 7%, 23% +/- 2%, respectively, group F P =.04, groups G and N P <.01). The number of arterioles 20 to 100 microm in diameter was increased to a greater extent in group FG than in groups F, G, and N (23 +/- 5 arterioles/mm(2), 14 +/- 3 arterioles/mm(2), 10 +/- 1 arterioles/mm(2), 4 +/- 2 arterioles/mm(2), respectively), with the differences being significant. CONCLUSIONS: These results show that bypass from the gastroepiploic artery to coronary arteries can be achieved without surgical anastomosis through slow release of basic fibroblast growth factor in this rabbit acute myocardial infarction model. This new revascularization concept, biologic coronary artery bypass grafting, could be applicable for revascularizing many tiny coronary vessels in patients who are difficult to treat with conventional surgery or catheter intervention.