A novel electron paramagnetic resonance spin-probe technique demonstrates the relation between the production of hydroxyl radicals and ischemia-reperfusion injury.

OBJECTIVE: Many previous studies have suggested an increase in hydroxyl radical (OH) production after myocardial ischemia-reperfusion; however, traditional techniques have not been able to conclusively prove this phenomenon. We investigated whether the production of OH was increased during myocardial reperfusion using a novel electron paramagnetic resonance (EPR) technique using an OH-specific spin probe. An OH scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), was used to examine the relationship between OH production and post-ischemic functional recovery or the degree of myocardial injury. METHODS: We used an isolated rabbit-heart preparation perfused with support-rabbit blood, and the heart was reperfused after normothermic global ischemia. Heart samples were reacted with the OH-specific spin probe, 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl (hydroxyl-TEMPO). The rate of decay of the EPR signal showed OH production. We investigated the rate of EPR signal decay and cardiac function. RESULTS: The rate of signal decay was significantly increased just after reperfusion compared with that of pre-ischemia (2.00×10(-2)±0.77×10(-2)min(-1) vs 0.11×10(-2)±0.02×10(-2)min(-1), p<0.01). Administration of MCI-186 reduced the rate of decay to 0.86×10(-2)±0.14×10(-2)min(-1) just after reperfusion (p<0.01). Cardiac function was significantly improved 60 min after reperfusion using MCI-186 compared without MCI-186 (left ventricular developed pressure was 95±9 mm Hg vs 60±6 mm Hg and the first derivative of the left ventricular pressure (dP/dt) was 1843±200 mm Hg s(-1) vs 1182±127 mm Hg s(-1)). CONCLUSIONS: A novel EPR spin-probe technique demonstrated the relation between the production of OH and ischemia-reperfusion injury. We confirmed that OH production influenced cardiac function and myocardial ischemia-reperfusion injury.

Rapid two-stage Starnes procedure for a symptomatic neonate with Ebstein anomaly.

We present a rapid two-stage Starnes procedure for a seriously symptomatic neonate with the prenatal diagnosis of Ebstein anomaly. At 16 hours after birth, we performed an emergency operation consisting of main pulmonary artery ligation, plication of the right atrial and right ventricular wall, modified Blalock-Taussig shunt, and patent ductus arteriosus ligation, without cardiopulmonary bypass. At age 12 days, we then performed the Starnes procedure using a glutaraldehyde-treated autologous pericardial patch with a 4-mm fenestration to close the tricuspid valve orifice. The infant's postoperative course was excellent. A rapid two-stage Starnes procedure is useful for treating a seriously symptomatic neonate with Ebstein anomaly.

Pulmonary artery banding for functionally single ventricles: impact of tighter banding in staged Fontan era.

BACKGROUND: In this study, we assessed our surgical strategy, tighter pulmonary artery banding (PAB) during the neonatal period, as an initial step followed by early application of bidirectional cavopulmonary shunts (BCPS) in infancy, to treat functionally single ventricles with unobstructed pulmonary blood flow. METHODS: On the basis of our surgical strategy, 68 consecutive patients underwent PAB and were divided into two groups, group 1 (January 1990 to June 2003; n = 30) and group 2 (July 2003 to August 2008; n = 38). The median age at PAB was 45 days in group 1 and 9 days in group 2. The circumference of the bands was significantly shorter in group 2 than in group 1, corresponding to the patient's weight in kg plus 19.0 +/- 0.6 mm in group 1 or 17.0 +/- 0.3 mm in group 2 (p = 0.003). RESULTS: Cardiac catheterization before the right heart bypass operation showed that the pulmonary artery index (group 1, 322 +/- 29; group 2, 283 +/- 27 mm(2)/m(2); p = 0.01), pulmonary resistance index (group 1, 2.4 +/- 0.2; group 2, 1.9 +/- 0.1 U x m(2); p = 0.03), and ventricular end-diastolic volume (group 1, 212 +/- 19%; group 2, 166 +/- 9%; p = 0.04) were significantly different between the two groups. The rates for achievement of right heart bypass at 12 months (group 1, 19%; group 2, 81%; p < 0.01) and survival at 3 years (group 1, 70%; group 2, 87%; p = 0.04) were significantly higher in group 2 than in group 1. CONCLUSIONS: Our present strategy could prevent volume overload and improve the achievement and survival rates of right heart bypass operations.

Staged surgical approach in neonates with a functionally single ventricle and arch obstruction: pulmonary artery banding and aortic arch reconstruction before placement of a bidirectional cavopulmonary shunt in infants.

The success rate of right-heart bypass surgery in patients with a functionally single ventricle (f-SV) and systemic obstruction is low. In patients with a high risk of subaortic stenosis, we performed an initial step of pulmonary artery banding (PAB) and arch reconstruction before placing a bidirectional cavopulmonary shunt (BCPS) in infants with or without Damus-Kaye-Stansel (DKS) anastomosis. We assessed the success of right-heart bypass surgery. Between October 2003 and August 2008, we performed surgery in 19 neonates (median age 5 days) with f-SV and arch obstruction. Extended aortic arch anastomosis, with or without distal arch augmentation, was performed in 10 patients, and subclavian flap aortoplasty was performed in 9 patients. The circumference of the PAB was determined as the individual patient's body weight in kilograms plus 16.2 +/- 3.7 mm. Eighteen of 19 infants (95%) underwent successful BCPS placement at a median age of 7.8 months. DKS anastomosis was performed concomitantly during BCPS placement in 11 infants in whom subaortic stenosis was morphologically suspected but not demonstrated physiologically. As our first-stage operation, arch reconstruction plus PAB provided high success rates for right-heart bypass operations. This strategy is not leading, but it is a reliable approach for progression along a Fontan pathway.

Surgical treatment of an infant with myocardial ischemia due to an anomalous origin of the right coronary artery from the main pulmonary artery: report of a case.

An anomalous origin of the right coronary artery from the main pulmonary artery (ARCAPA) is a rare cardiac malformation, and only three cases of isolated ARCAPA in patients younger than 2 years of age have been reported. This report describes the surgical treatment of a 12-month-old girl with myocardial ischemia due to ARCAPA. The diagnosis was made by echocardiography. A reimplantation of the aberrant coronary artery was performed, and the patient had a successful postoperative course.

A symptomatic neonate with tetralogy of Fallot, an absent pulmonary valve, and a single coronary artery with a major fistula.

We present a case with a rare combination of tetralogy of Fallot with an absent pulmonary valve, and a single coronary artery with a major fistula to the main pulmonary artery. Myocardial ischemia developed in response to increasing shunt flow through the coronary fistula, resulting in heart failure. We ligated the coronary fistula and plicated the anterior wall of the dilated pulmonary arteries during the neonatal period. Complete repair through a transatrial-transpulmonary approach was performed at the age of 17 months. The postoperative course was excellent and the patient maintained a stable hemodynamic and respiratory state with no evidence of myocardial ischemia.

Bland-White-Garland syndrome with ventricular septal defect: late presentation.

Bland-White-Garland syndrome has been reported generally to occur in an isolated lesion. Here, we report a case of Bland-White-Garland syndrome associated with a ventricular septal defect. Late onset of myocardial ischemia was noted in this patient, which we think is related to increased coronary steal due to regression of pulmonary hypertension caused by narrowing of the ventricular septal defect. At surgery, we temporally occluded the left main coronary trunk to cease the coronary steal phenomenon and augment the left coronary flow. Direct implantation of the left coronary artery and closure of the ventricular septal defect were performed. The postoperative course was excellent with no evidence of myocardial ischemia.

Clinical results of commissure plication annuloplasty for mitral regurgitation in children.

PURPOSE: We evaluated the clinical results of commissure plication annuloplasty for mitral regurgitation (MR) in children. METHODS: Twenty-eight patients underwent a valve repair with commissure plication annuloplasty for MR from 1988 to 2005. The mean age was 2.7 +/- 3.3 years. Several appropriate techniques were combined (cleft closure in 5 patients, chordal shortening in 2 patients, artificial chordal replacement in 4 patients, leaflet fixation in 2 patients, and so on). The mean follow-up period was 6.2 years. RESULTS: There was one operative death (3.6%) and no late deaths. Two patients underwent a second repair 19 and 23 months after their initial repairs. The actuarial freedom from the reoperation rate was 90.4% +/- 0.6% at 10 years. The freedom from moderate MR or more was shown to decrease over time, 87.8% +/- 0.7% at 5 years and 78.0% +/- 11.0% at 10 years. Furthermore, the 10-year freedom from mild MR or more was 56.5% +/- 11.9%. A progression of MR was seen. Most of the residual or recurrent MR cases weighed less than 10 kg at operation. CONCLUSIONS: The combination of commissure plication annuloplasty and several appropriate techniques provided adequate results for MR in children. Since a progression of MR was observed, a careful follow-up is therefore needed in such cases.

Impact of 3-mm Blalock-Taussig shunt in neonates and infants with a functionally single ventricle.

Functionally single ventricle (f-SV) is susceptible to volume overload. Atrioventricular valve regurgitation (AVVR) tends to develop and ventricular function deteriorates due to excessive pulmonary blood flow following modified Blalock-Taussig shunt (mBTS). On the other hand, a small caliber graft has risks of early obstruction and poor growth of pulmonary vascular beds. We assessed the effect of mBTS with a 3-mm graft to circumvent volume overload in f-SV on achievement of the right heart bypass. Eleven neonates and infants with f-SV at the median age of 24 days underwent mBTS using a 3-mm graft between August 2004 and June 2007. There were no early deaths, but there was one late death. All survivors achieved bidirectional cavopulmonary shunt (BCPS) at 4.2 months after mBTS. Cardiac catheterization demonstrated sufficient growth of the pulmonary artery (pulmonary artery index, 268+/-98 cm(2)/m(2)), low pulmonary vascular resistance (1.4+/-0.9 U.m(2)). The AVVR remained mild or less. Ventricular end-diastolic volume and ejection fraction were 171+/-61% of the normal value and 64+/-6%, respectively. We conclude that a 3-mm mBTS was useful in preventing f-SV from volume overload and was effective for growing good pulmonary vasculature and achieving a right heart bypass.

Surgical results of anomalous origin of the right pulmonary artery from the ascending aorta including reoperation for infrequent complications.

BACKGROUND: We evaluated the results of surgery for an anomalous origin of the right pulmonary artery from the ascending aorta. METHODS: From August 1986 to December 2005, 8 children (6 neonates) aged 7 to 180 days (mean, 35 +/- 59 days) with anomalous origin of the right pulmonary artery from the ascending aorta underwent surgical repair at our institute. All except one child, who had the distal form, had the proximal form. Cardiac catheterization showed that the left pulmonary artery to systemic pressure ratio was 1.0 or more. Surgery was performed by direct anastomosis in 7 patients and by graft interposition in 1. RESULTS: There were no operative or late deaths. All patients postoperatively underwent cardiac catheterization that showed decreased left pulmonary artery to systemic pressure ratio ranging from 0.2 to 0.6. Follow-up periods ranged from 2 months to 13 years. We undertook reoperations for two infrequent postoperative causes. One patient exhibited significant supravalvar aortic stenosis and required patch enlargement of the ascending aorta 3 years after operation. The other patient (with the distal form) needed a reoperation after 1 month because of progressive stenosis at the anatomic site. Graft interposition was performed, and histopathologic examination showed that the tissue from the stenotic region looked like that of a ductus. CONCLUSIONS: We undertook surgical repair for anomalous origin of the right pulmonary artery from the ascending aorta. Pulmonary hypertension was improved in all patients. Careful follow-up was necessary to detect supravalvar aortic and anastomotic stenosis early and late after operation.

Surgical experience of cardiac tumors: early and late results.

PURPOSE: Cardiac tumors include benign and malignant neoplasms that arise within the cardiac chambers or myocardium. This study summarizes our surgical experiences with cardiac tumors. METHODS: Between 1975 and 2003, 51 patients with cardiac tumors were surgically treated. RESULTS: Myxomas. Forty-seven cardiac myxomas were excised in 46 patients with an average age of 51.7 +/- 18 years. The preoperative symptoms included congestive heart failure (37%) and embolism (30%). The incidence of preoperative embolization was significantly higher in the gelatinous and lobated myxomas than in the solid and smooth form (P = 0.017). The early mortality rate was 2.2%. Although the late mortality rate was 9.7%, no patients died from cardiological causes (mean follow-up, 11.2 years). Only 1 patient required surgery for recurrence. Benign nonmyxomatous tumors. Three patients with a mean age of 26.3 +/- 19.0 years showed benign nonmyxomatous tumors. There were no perioperative or late deaths. Malignant tumors. Two patients were diagnosed to have malignant tumors and although there was no perioperative death, both died postoperatively within 6 months. CONCLUSIONS: Cardiac myxomas and nonmyxomatous benign cardiac tumors show excellent results after a surgical excision, with a low morbidity and mortality. A surgical resection should thus be considered as a treatment option for patients with malignant tumors.

The UW solution has greater potential for longer preservation periods than the Celsior solution: comparative study for ventricular and coronary endothelial function after 24-h heart preservation.

OBJECTIVE: Improvement of long-term heart preservation methods would potentially increase the donor pool and improve survival. We compared the efficacies of the University of Wisconsin (UW) and Celsior solutions on ventricular and endothelial functions after 24-h preservation. METHODS: We used an isolated heart preparation perfused with blood. The heart was excised from a rabbit, stored for 24 h in the UW or Celsior solution, and then perfused with blood from a support-rabbit. We evaluated cardiac output and coronary endothelial function. RESULTS: The Frank-Starling curve showed a significant left and upward shift in the UW group compared with that in the Celsior group (p<0.01). There were no significant differences between the groups for the coronary blood flow in response to sodium nitroprusside or acetylcholine. The serum creatine kinase MB level after reperfusion was significantly lower in the UW group than in the Celsior group (10.7+/-1.4 ng/mL vs 30.4+/-5.4 ng/mL, p<0.01), whereas lipid peroxide levels did not differ significantly between the two groups. CONCLUSIONS: The UW group showed better left ventricular function than the Celsior group, indicating that the UW solution has greater potential for long-term preservation than Celsior solution.

A comparative study of cardiac preservation with Celsior or University of Wisconsin solution with or without prior administration of cardioplegia.

BACKGROUND: We have previously reported the cardiac functional and metabolic benefits of administration of extracellular-type cardioplegia before preservation with University of Wisconsin solution. Celsior solution was designed to be used both as an arresting solution and a storage solution for heart transplantation. The objective of the present study is to compare cardiac function of hearts arrested and preserved with Celsior solution to hearts arrested with cardioplegia followed by preservation with UW solution. METHODS: Rabbit hearts were divided into 4 groups: in the Celsior group, hearts were arrested and preserved with Celsior solution; in the C-Celsior group, hearts were arrested by an extracellular-type cardioplegia and preserved with Celsior solution; in the UW group, hearts were arrested and stored in University of Wisconsin solution; and, in the C-UW group, hearts were arrested with extracellular-type cardioplegia and stored in University of Wisconsin solution. After 6 hours of preservation, cardiac function was measured using modified Frank-Starling curves in the isolated blood-perfused working heart. RESULTS: Cardiac function in the Celsior group was inferior to that in both the C-UW group and UW group. The C-Celsior group demonstrated inferior cardiac function compared with the Celsior group (p < 0.01), whereas no significant difference was observed between the C-UW and UW groups. CONCLUSIONS: Celsior solution did not surpass UW solution regardless of the use of cardioplegia. Further studies are required to develop optimal solution for use as both an arresting solution and a storage solution.

Angiotensin II type 1 receptor antagonist protects ventricular and coronary endothelial function after 24-hour heart preservation.

BACKGROUND: Angiotensin II type 1 (AT1) receptor antagonists may enhance the cyclic guanosine monophosphate-nitric oxide system and thereby attenuate ventricular and coronary endothelial dysfunction after heart preservation. METHODS: We used an isolated rabbit heart preparation perfused with blood from a support rabbit. The rabbit heart was excised, stored for 24 hours, and then perfused with blood from a support rabbit that was treated with an AT1 receptor antagonist (telmisartan; 5 mg/kg) or solvent. We evaluated the cardiac output with the working preparation, and coronary blood flow and coronary endothelial function with the Langendorff preparation. In addition, we measured the serum nitric oxide level in the coronary effluent. RESULTS: The Telmisartan Group showed higher plasma angiotensin II levels (928.6 +/- 136.2 vs 271.6 +/- 81.6 pg/ml, p < 0.01), better cardiac output (116.2 +/- 5.4 vs 88.8 +/- 7.1 ml/min, p < 0.05), and higher coronary blood flow (25.0 +/- 2.2 vs 14.9 +/- 1.3 ml/min, p < 0.01). The coronary blood flow in response to acetylcholine was higher in the Telmisartan Group (47.8 +/- 3.9 vs 28.0 +/- 2.1 ml/min, p < 0.01), but there was no difference in response to sodium nitroprusside. The Telmisartan Group showed higher serum nitric oxide levels in the coronary effluent (33.9 +/- 4.6 vs 20.6 +/- 3.3 mumol/liter, p < 0.05). CONCLUSIONS: Treatment with the AT1 receptor antagonist improved ventricular and endothelial function after 24-hour heart preservation. These data imply that AT1 activation plays a critical role in reperfusion injury. AT1 receptor blockade may be a promising strategy for long-term heart preservation.

Endothelin-1 receptor antagonist prevents deterioration of left ventricular function and coronary flow reserve in brain-dead canine heart.

BACKGROUND: Rapid hemodynamic deterioration is caused by induction of brain death, but the exact mechanism is still uncertain. The aim of this study was to investigate the contribution of endothelin-1 by using endothelin-1 receptor antagonist (TAK-044) in a canine brain-death model. METHODS: Dogs were divided into 2 groups: (1) the TAK group, in which TAK-044 was intravenously injected 30 minutes before brain-death induction at a dose of 3 mg/kg; and (2) the control group. Brain death was induced by rapid inflation of a sub-durally placed balloon catheter. Left ventricular function and coronary flow reserve was compared between the 2 groups. RESULTS: Brain death caused a transient hyperdynamic response followed by hemodynamic deterioration after 60 minutes in both groups. Left ventricular function, evaluated by the slope of the end-systolic pressure-volume relation was significantly decreased from 7.7 +/- 0.6 to 3.7 +/- 0.3 mm Hg/ml (p < 0.01) in the control group, but was not decreased in the TAK group (7.7 +/- 0.8 to 7.3 +/- 0.9 mm Hg/ml, p = 0.75). Coronary flow reserve, measured by direct injection of acetylcholine (3 microg) into the coronary artery, was significantly reduced at 60 minutes after brain death in the control group (264.8% to 176.6%, p < 0.01), but not in the TAK group (291.2% to 301.3%, p = 0.84). Exactly the same results were obtained when sodium nitroprusside (SNP; 100 microg) was administered. CONCLUSIONS: TAK-044 can prevent the deterioration of left ventricular function and coronary flow reserve that follows induction of brain death, suggesting that endothelin-1 could play an important role in hemodynamic deterioration by impairment of coronary microcirculation after brain death.

Three-layered synthetic pericardial substitutes reduce postoperative pericardial adhesions.

BACKGROUND: The development of postoperative pericardial adhesions increases the risk of cardiac reoperations. The purpose of this study was to test a new pericardial substitute (UBE sheet; UBE Industries, Ltd, Tokyo, Japan) that consists of 3 layers, namely, a middle layer of polyester inserted between 2 layers of silicone-urethane copolymer. METHODS: Before implantation into the animals, platelet adhesion to the UBE sheet was evaluated in vitro. In the canine model, the UBE sheet (group I; n = 6) was implanted for 3 months. The development of adhesions, epicardial reactions, the shrink ratio of the patch, and macrophage infiltration to the epicardium with histologic examination were evaluated. As a control, an expanded polytetrafluoroethylene sheet (group II; n = 5) was implanted in the same manner. RESULTS: Scanning electron microscopy of the platelets adhered to the sheet showed that the UBE sheet was superior in biocompatibility compared with the expanded polytetrafluoroethylene sheet. In the canine study, group I showed fewer adhesions than group II (median [25th percentile, 75th percentile]: 0.0 [0.0, 0.0] vs 1.0 [1.0, 2.3]; P = .003; Mann-Whitney U test), fewer epicardial reactions (1.75 [1.0, 3.0] vs 3.0 [3.0, 3.0]; P = .034), and a smaller shrink ratio (8.0% [5.5%, 12.4%] vs 31.7% [30.0%, 44.8%]; P = .006). Immunohistologic studies showed fewer macrophage infiltrations (86 [56.8, 139.3] vs 201 [161.0, 276.5] in 3 fields; P = .045) into the epicardium of group I. CONCLUSIONS: The new 3-layered pericardial substitute clearly reduced adhesion formation. We concluded that this sheet may cause fewer adhesions and a less severe inflammatory reaction after cardiac surgery, thereby facilitating safe adhesiolysis reoperation.

Extracorporeal cardiac shock wave therapy markedly ameliorates ischemia-induced myocardial dysfunction in pigs in vivo.

BACKGROUND: Prognosis of ischemic cardiomyopathy still remains poor because of the lack of effective treatments. To develop a noninvasive therapy for the disorder, we examined the in vitro and vivo effects of extracorporeal shock wave (SW) that could enhance angiogenesis. METHODS AND RESULTS: SW treatment applied to cultured human umbilical vein endothelial cells significantly upregulated mRNA expression of vascular endothelial growth factor and its receptor Flt-1 in vitro. A porcine model of chronic myocardial ischemia was made by placing an ameroid constrictor at the proximal segment of the left circumflex coronary artery, which gradually induced a total occlusion of the artery with sustained myocardial dysfunction but without myocardial infarction in 4 weeks. Thereafter, extracorporeal SW therapy to the ischemic myocardial region (200 shots/spot for 9 spots at 0.09 mJ/mm2) was performed (n=8), which induced a complete recovery of left ventricular ejection fraction (51+/-2% to 62+/-2%), wall thickening fraction (13+/-3% to 30+/-3%), and regional myocardial blood flow (1.0+/-0.2 to 1.4+/-0.3 mL x min(-1) x g(-1)) of the ischemic region in 4 weeks (all P<0.01). By contrast, animals that did not receive the therapy (n=8) had sustained myocardial dysfunction (left ventricular ejection fraction, 48+/-3% to 48+/-1%; wall thickening fraction, 13+/-2% to 9+/-2%) and regional myocardial blood flow (1.0+/-0.3 to 0.6+/-0.1 mL x min(-1) x g(-1)). Neither arrhythmias nor other complications were observed during or after the treatment. SW treatment of the ischemic myocardium significantly upregulated vascular endothelial growth factor expression in vivo. CONCLUSIONS: These results suggest that extracorporeal cardiac SW therapy is an effective and noninvasive therapeutic strategy for ischemic heart disease.

Transfection with a dominant-negative inhibitor of monocyte chemoattractant protein-1 gene improves cardiac function after 6 hours of cold preservation.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1), a potent chemotactic factor for monocytes, is induced during ischemia-reperfusion. As monocytes might play an important causative role in reperfusion injury, we investigated if inhibition of monocyte activation could attenuate ischemia-reperfusion injury and thereby improve cardiac preservation. To inhibit monocyte activation, we transfected a dominant-negative inhibitor of MCP-1 (7ND) gene in an animal model. METHODS AND RESULTS: We used an isolated rabbit heart preparation perfused with support-rabbit blood and transfected 7ND genes to skeletal muscle of the support rabbits (n=7) using electroporation technique; causing an elevation of serum 7ND level to 20+/-7 pg/mL at 5 days after transfection. Animals receiving empty plasmid served as controls (n=7). Five days after transfection, hearts from other rabbits were excised, stored in UW solution for 6hours, and perfused with blood from transfected support rabbits. The 7ND group showed better cardiac output (128.7+/-17.9 versus 81.6+/-19.8 mL/min; P<0.01), lower serum CK-MB levels (5.0+/-1.8 versus 11.1+/-2.9 ng/mL; P<0.01), lower serum IL-1beta levels (257.2+/-23.2 versus 311.2+/-37.4pg/mL; P<0.05), and lower serum TNF-alpha levels (19.0+/-8.4 versus 35.1+/-13.0pg/mL; P<0.05). The numbers of infiltrating cells in myocardium were significantly reduced in the 7ND group. CONCLUSIONS: Inhibition of MCP-1 with 7ND gene transfection reduced cytokine activation, attenuated myocardial damage, and improved cardiac function after 6 hours of preservation. These results show that MCP-1 plays an important role in ischemia-reperfusion injury.

Impairment of coronary flow reserve and left ventricular function in the brain-dead canine heart.

OBJECTIVE: The mechanisms of cardiac dysfunction after brain death, which are thought to be mainly associated with massive catecholamine release, have not been fully elucidated, especially with respect to the coronary circulation. The aim of this study was to investigate the changes in function of the coronary artery and its contribution to hemodynamic deterioration in a canine brain death model. METHODS: Brain death was induced by rapid inflation of a subdurally placed balloon catheter. Hemodynamic measurements including assessment of left ventricular contractility using pressure-volume relations and biochemical analyses of blood samples were performed in seven dogs. Coronary flow reserve in the same brain death model was assessed by changes in coronary flow and resistance induced by administering a vasodilator directly into the coronary artery in another eight dogs. RESULTS: A hyperdynamic response was transiently observed after induction of brain death, followed by decreases in arterial pressure, cardiac output, and coronary blood flow. Parameters of left ventricular contractility as measured by pressure-volume relations had significantly deteriorated by 60 min after brain death. Percent changes in coronary flow by administration of acetylcholine and sodium nitroprusside were 272 and 209%, respectively, before brain death; these were decreased to 178 and 145% at 30 min after brain death, and to 192 and 153% at 60 min. Coronary resistance ratios were also significantly increased at 30 and 60 min after brain death. CONCLUSIONS: Impairment of coronary flow reserve was found in the brain-dead canine heart. This impaired coronary circulation may constitute a disadvantage of prevention and recovery of cardiac dysfunction after induction of brain death.