Vincenzo Gallucci: Memories of a Surgeon, Scientist, and Teacher.

Thirty years ago, Vincenzo Gallucci, MD, head of the Cardiovascular Surgery Institute of the University of Padua Medical School in Italy, died in a car accident at the age of 55 years. Vincenzo Gallucci was one of the most authoritative Italian cardiac surgeons, a fine, gentle, and extremely talented surgeon. He is credited with the first implant of a glutaraldehyde-fixed, stented porcine Hancock bioprosthesis in 1970 and with the first orthotopic heart transplantation performed in Italy in 1985. After 30 years, the memory of a great surgeon, scientist, and teacher is still alive, particularly in those who received his important heritage.

Current management of double-outlet left ventricle: towards biventricular repair in infancy.

BACKGROUND: Double-outlet left ventricle (DOLV) is an extremely rare type of ventriculoarterial connection, mostly reported anecdotally with wide variations in morphology, surgical strategy and clinical outcome. The aim of the present study was to define current morbidity and mortality of biventricular repair and discuss surgical management in infancy. METHODS: Inclusion criteria were English literature publication; balanced ventricular development and completion of biventricular repair. Institutional experience was also reported. Study end points were survival and freedom from cardiovascular events. Univariate analysis to identify risk factors for complications was performed. RESULTS: During a 45-year interval, 37 cases of DOLV were identified. Median age at repair was 48 months (range 0.3-336); seven patients were infants. Extracardiac repair was performed in 21 (57%) patients, right ventricular outflow patch in seven, pulmonary translocation in six, and intraventricular repair in three. There were three (8%) hospital deaths, due to right heart failure, and seven (21%) patients experienced 10 perioperative complications. Univariate analysis showed year of operation (P = 0.02) and outflow patch technique (P = 0.003) as risk factors for hospital morbidity and mortality. During a median follow-up of 26 months (range 1-192), there was one death and seven reoperations. Ten-year survival and freedom from adverse cardiovascular events were 87 ±â€Š6 and 70 ±â€Š10%, respectively. CONCLUSION: Although seldom reported in the past, repair of DOLV in infancy does not increase surgical risk. Early and late morbidity are mostly due to right heart complications and more common after right ventricular outflow patch repair. Paucity of follow-up information may underestimate actual late adverse event rate.

Anterior mitral annulus caseoma: as benign as posterior counterparts?

Mitral annular caseoma is a common incidental finding involving the posterior annulus. It has an innocent nature, with the exception of its endocarditic degeneration and/or a stenotic functional effect when exophytic. We report an exceptionally rare isolated anterior mitral annular caseoma involving also the anterior mitral leaflet and affecting its physiologic systolic movement, thus resulting in a restricting anterior leaflet motion responsible for mitral insufficiency. The case was successfully treated by complex mitral valve repair.

European multicenter experience with valve-sparing reoperations after the Ross procedure.

BACKGROUND: Autograft valve preservation at reoperation may conserve some of the advantages of the Ross procedure. However, results of long-term follow-up are lacking. In this retrospective multicenter study, we present our experience with valve-sparing reoperations after the Ross procedure, with a focus on long-term outcome. METHODS: A total of 86 patients from 6 European centers, who underwent valve-sparing reoperation after the Ross procedure between 1997 and 2013, were included in the study. RESULTS: Reoperation was performed a median of 9.1 years after the Ross procedure in patients with a median age of 38.4 years (interquartile range: 27.1-51.6 years). Preoperative severe autograft regurgitation (grade ≥3) was present in 46% of patients. In-hospital mortality was 1%. During a median follow-up of 4.3 years, 3 more patients died of noncardiac causes, resulting in a cumulative survival at 8 years of 89% (95% confidence interval: 65%-97%). Fifteen patients required a reintervention after valve-sparing reoperation, mostly owing to prolapse or retraction of autograft cusps. Freedom from reintervention was 76% (95% confidence interval: 57%-87%) at 8 years. The reintervention hazard was increased in patients who had isolated and/or severe aortic regurgitation at valve-sparing reoperation. In patients without reintervention after valve-sparing autograft reoperation (n = 63), severe aortic regurgitation was present in 3% at last follow-up. CONCLUSIONS: Valve-sparing autograft reoperations after the Ross procedure carry a low operative risk, with acceptable reintervention rates in the first postoperative decade. Patients with isolated and/or severe autograft regurgitation have an increased hazard of reintervention after valve-sparing reoperation; for these patients, careful preoperative weighing of surgical options is required.

Is it possible to assess the best mitral valve repair in the individual patient? Preliminary results of a finite element study from magnetic resonance imaging data.

OBJECTIVES: Finite element modeling was adopted to quantitatively compare, for the first time and on a patient-specific basis, the biomechanical effects of a broad spectrum of different neochordal implantation techniques for the repair of isolated posterior mitral leaflet prolapse. METHODS: Cardiac magnetic resonance images were acquired from 4 patients undergoing surgery. A patient-specific 3-dimensional model of the mitral apparatus and the motion of the annulus and papillary muscles were reconstructed. The location and extent of the prolapsing region were confirmed by intraoperative findings, and the mechanical properties of the mitral leaflets, chordae tendineae and expanded polytetrafluoroethylene neochordae were included. Mitral systolic biomechanics was simulated under preoperative conditions and after 5 different neochordal procedures: single neochorda, double neochorda, standard neochordal loop with 3 neochordae of the same length and 2 premeasured loops with 1 common neochordal loop and 3 different branched neochordae arising from it, alternatively one third and two thirds of the entire length. RESULTS: The best repair in terms of biomechanics was achieved with a specific neochordal technique in the single patient, according to the location of the prolapsing region. However, all techniques achieved a slight reduction in papillary muscle forces and tension relief in intact native chordae proximal to the prolapsing region. Multiple neochordae implantation improved the repositioning of the prolapsing region below the annular plane and better redistributed mechanical stresses on the leaflet. CONCLUSIONS: Although applied on a small cohort of patients, systematic biomechanical differences were noticed between neochordal techniques, potentially affecting their short- to long-term clinical outcomes. This study opens the way to patient-specific optimization of neochordal techniques.

Two decades of experience with the Ross operation in neonates, infants and children from the Italian Paediatric Ross Registry.

OBJECTIVE: Children undergoing Ross operation were expected to have longer autograft, but shorter homograft durability compared with adults. In order to define the outcome in the second decade after Ross operation in children, a nationwide review of 23 years of experience was undertaken. METHODS: 305 children underwent Ross operation in 11 paediatric units between 1990 and 2012. Age at surgery was 9.4±5.7 years, indication aortic stenosis in 103 patients, regurgitation in 109 and mixed lesion in 93. 116 (38%) patients had prior procedures. Root replacement was performed in 201 patients, inclusion cylinder in 14, subcoronary grafting in 17 and Ross-Konno in 73. RESULTS: There were 10 (3.3%) hospital and 12 late deaths (median follow-up 8.7 years). Survival was 93±2% and 89±3% and freedom from any reoperation was 76±3% and 67±6% at 10 and 15 years. 34 children had autograft 37 reoperations (25 replacement, 12 repair): three required transplantation after reoperation. Freedom from autograft reoperation was 86±3% and 75±6% at 10 and 15 years. 32 children had right heart redo procedures, and only 25 (78%) conduit replacements (15-year freedom from replacement, 89±4%). Prior operation (p=0.031), subcoronary implant (p=0.025) and concomitant surgical procedure (p=0.004) were risk factors for left heart reoperation, while infant age (p=0.015) was for right heart. The majority (87%) of late survivors were in NYHA class I, 68% free from medication and six women had pregnancies. CONCLUSIONS: Despite low hospital risk and satisfactory late survival, paediatric Ross operation bears substantial valve-related morbidity in the first two decades. Contrary to expectation, autograft reoperation is more common than homograft.

Neonatal repair of truncus arteriosus with "scimitar-like" mixed total pulmonary venous return.

The association between truncus arteriosus and total anomalous pulmonary venous return is exceedingly rare. Here described is a neonate presenting with a common arterial trunk and a previously unreported "scimitar-like" mixed total pulmonary venous return who underwent a successful one-stage repair. The unprecedented anatomic pattern of the systemic and pulmonary venous connection and the original surgical strategy are discussed.

Diabetic hearts have lower basal urocortin levels that fail to increase after cardioplegic arrest: association with increased apoptosis and postsurgical cardiac dysfunction.

OBJECTIVES: The present study investigated the cardioprotective role of urocortin (Ucn) and its relationship with protein kinase C (PKC)ε and PKCδ in patients with (DMPs) and without (NDMPs) diabetes mellitus after on-pump cardiac surgery (OPCS). The molecular mechanisms responsible for the reported worse outcomes of DMP after OPCS remain unknown. METHODS: Two sequential biopsy specimens were obtained from the right atrium of 27 DMPs and 22 NDMPs before and after cardiopulmonary bypass. RESULTS: Postcardioplegic induction of Ucn in NDMPs (P<.01) was not observed in the DMPs, whose precardioplegic Ucn levels were 50% lower than those in the NDMPs (P<.05). In the NDMPs, cardioplegic arrest increased PKCε mRNA and protein (P<.05); overexpression of PKCδ was not seen. In contrast, DMPs showed increased PKCδ expression (P<.01), with no change in PKCε. Apoptosis was more than twofold greater in the postcardioplegic samples from the DMPs than in those from the NDMPs. The apoptotic myocytes were Ucn negative and exhibited nuclear relocation of PKCδ. Enhanced PKCε/mitochondrial co-localization was observed in viable, Ucn-positive, myocytes. The leakage of troponin I documented in the DMPs was greater than that in the NDMPs, although the difference was not statistically significant (P=.06). Furthermore, despite a similar incidence of perioperative acute myocardial infarction, the DMPs did not show postoperative improvement of systolic or diastolic function, although that was seen in the NDMPs (P<.05). CONCLUSIONS: Cardioplegic arrest failed to induce in DMPs myocyte overexpression of Ucn or PKCε but was associated with induction and mitochondrial relocation of PKCδ, resulting in apoptosis. Failure to overexpress Ucn in the DMPs was associated with apoptosis and cardiac dysfunction and, thus, might contribute to worse postoperative outcomes.

Ventricular and pulmonary vascular remodeling induced by pulmonary overflow in a chronic model of pretricuspid shunt.

OBJECTIVES: Current preclinical models of pulmonary arterial hypertension do not reproduce the clinical characteristics of congenital heart anomalies. Aortocaval shunt is relevant to a variety of clinical conditions. The pathophysiology and possible determination of pulmonary hypertension in this model are still undefined. METHODS: A method to create a standardized and reproducible aortocaval shunt was developed in rats. After creation of the shunt, the animals were followed up for 20 weeks and a sham laparotomy was used as a control. The chronic effects of volume overload on the right and left ventricles and pulmonary hemodynamic modifications were evaluated by biventricular catheterization, echocardiography, and magnetic resonance. Pulmonary vascular changes were defined by histology. RESULTS: An increased right ventricular end-diastolic area was confirmed by echocardiography. Left ventricular overload and decreased biventricular ejection fraction were demonstrated by magnetic resonance after 20 weeks in the shunt group compared with the controls (left ventricle, 50% ± 5% vs 62% ± 3%, P = .029; right ventricle, 53% ± 2% vs 65% ± 2%, P = .036). Preload recruitable stroke work of left and right ventricles decreased after 20 weeks in shunt rats (left ventricle: 36 ± 7 vs 98 ± 5, P = .004; right ventricle: 19 ± 2 vs 32 ± 9, P = .047). At the same time point, catheterization showed that effective pulmonary arterial elastance was increased only in the shunt group (1.29 ± 0.20 vs 0.14 ± 0.06 mm Hg/µL; P = .004). Histology showed medial hypertrophy, small artery luminal narrowing, and occlusion. CONCLUSIONS: The aortocaval shunt model reliably produces right ventricular volume overload and secondary pulmonary hypertension. Due to a combination of left ventricular dysfunction and pulmonary overflow, the pulmonary hypertension produced shows features similar to those found in patients with chronic atrial-level shunt.

Chronic overcirculation-induced pulmonary arterial hypertension in aorto-caval shunt.

Pulmonary arterial hypertension is a common complication of congenital heart defects with left-to-right shunts. Current preclinical models do not reproduce clinical characteristics of shunt-related pulmonary hypertension. Aorto-caval shunt was firstly described as a model of right ventricle volume overload. The pathophysiology and the possible determination of pulmonary arterial hypertension of different periods of shunt exposure are still undefined. A method to create standardized, reproducible aorto-caval shunt was developed in growing rats (260±40 g). Three groups of animals were considered: shunt exposure for 10 weeks, shunt exposure for 20 weeks and control (sham laparotomy). Echocardiography and magnetic resonance revealed increased right ventricular end diastolic area in shunt at 10 weeks compared to control. Hemodynamic analysis demonstrated increased right ventricular afterload and increased effective pulmonary arterial elastance (Ea) in shunt at 20 weeks compared to control (1.29±0.20 vs. 0.14±0.06 mmHg/µl, p=0.004). At the same time point, the maximal slope of end-systolic pressure-volume relationship (Ees) decreased (0.5±0.2 mmHg/ml vs. 1.2±0.3, p<0.001). Consequently, right ventricular-arterial coupling was markedly deteriorated with a ≈50% decrease in the ratio of end-systolic to pulmonary artery elastance (Ees/Ea). Finally, left ventricular preload diminished (≈30% decrease in left ventricular end-diastolic volume). Histology demonstrated medial hypertrophy and small artery luminal narrowing. Chronic exposure to aorto-caval shunt is a reliable model to produce right ventricular volume overload and secondary pulmonary arterial hypertension. This model could be an alternative with low mortality and high reproducibility for investigators on the underlying mechanisms of shunt-related pulmonary hypertension.

First-time, isolated surgical aortic valve replacement after prior coronary artery bypass surgery: results from the RECORD multicenter registry.

BACKGROUND: This multicenter study was undertaken to determine the immediate and long-term outcomes in patients undergoing a primary surgical aortic valve replacement (AVR) who had a previous coronary artery bypass graft surgery with patent grafts. METHODS: One hundred and thirteen consecutive patients (mean EuroSCORE II, 10.3 ± 7.7%, median 8.0%) who underwent first-time isolated AVR after coronary artery bypass grafting (CABG) were the subjects of this multicenter study. The procedure was performed through a full sternotomy in 95.7% of cases, a patent internal mammary artery graft was clamped in 76.6% of patients. The temperature of cardioplegia was ≤12 °C in 62.8% of patients and systemic temperature was <32 °C in 23.9% of patients. RESULTS: Thirty-day mortality was 4.4%. Stroke was observed in 8.0% of patients, low cardiac output syndrome in 14.1%, prolonged tracheal intubation in 20.8%, and intensive care unit stay was longer than five days in 19.5% of patients. Among patients with a patent internal mammary graft (91 patients), clamping of this graft (5.7% vs. 0%, p = 0.57) was associated with a nonsignificant trend toward increased 30-day mortality. One-, three- and five-year survival rates were 91.5%, 90.4%, and 88.4%, respectively. CONCLUSIONS: Patients undergoing isolated AVR after prior CABG have a good immediate and late survival. A history of prior CABG should not be considered an absolute indication for transcatheter AVR.

In which patients is transcatheter aortic valve replacement potentially better indicated than surgery for redo aortic valve disease? Long-term results of a 10-year surgical experience.

BACKGROUND: Redo aortic valve replacement procedures have been reduced by the growing practice of trans-catheter aortic valve-in-valve procedures. We analyzed our long-term results of redo aortic valve replacement procedures during a 10-year period in an effort to define subgroups in which trans-catheter aortic valve-in-valve procedures may be better than surgery. METHODS: From 2002 to 2010, 131 redo aortic valve replacement procedures with at least 18 months of follow-up were prospectively enrolled. Hospital and follow-up outcome of the entire population and of high-risk subgroups were evaluated. RESULTS: Hospital mortality was 2.3%, major re-entry complications were seen in 1.5%, re-exploration for bleeding was seen in 9.2%, perioperative low cardiac output state (ie, low cardiac output syndrome) was seen in 9.9%, stroke was seen in 3.1%, prolonged ventilation was seen in 18.3%, pneumonia was seen in 4.6%, acute renal insufficiency was seen in 11.5%, intra-aortic counterpulsation (intra-aortic balloon pump) was seen in 9.2%, renal replacement therapy was seen in 4.6%, need for transfusions was seen in 60.3%, and permanent pacemaker implantation was seen in 2.3%. One hundred twenty-month actuarial survival, freedom from acute heart failure, reinterventions, stroke, and thromboembolisms were 61.5% ± 8.6%, 62.9% ± 6.9%, 97.8% ± 1.5%, 93.2% ± 3.0%, and 91.2% ± 3.2%, respectively. Patients aged >75 years had similar outcome to younger patients (nonsignificant P for all). Endocarditis resulted in higher hospital mortality (P = .034), low cardiac output state (P < .0001), intra-aortic balloon pump (P < .0001), prolonged ventilation (P = .011), pneumonia (P = .049), acute renal insufficiency (P = .004), lower actuarial survival (log-rank P = .0001), freedom from acute heart failure (P = .002), and re-intervention (P = .003). New York Heart Association functional class IV at admission resulted in a higher incidence of low cardiac output state (P < .0001), intra-aortic balloon pump (P = .0001), prolonged ventilation (P < .0001), pneumonia (P = .015), and a lower actuarial freedom from re-intervention (P = .0001). Higher need for permanent pacemaker implantation (P = .015) and lower freedom from acute heart failure (P = .019) emerged after urgencies/emergencies. CONCLUSIONS: Redo aortic valve replacement procedures achieves good results, especially in nonendocarditic or elective cases, and young or New York Heart Association functional class I/II patients. Indeed, endocarditis significantly affects outcome. New York Heart Association functional class IV and nonelective procedures might benefit from trans-catheter aortic valve-in-valve procedures.

Functional mitral regurgitation: a 30-year unresolved surgical journey from valve replacement to complex valve repairs.

Functional mitral regurgitation remains one of the most complex and controversial aspect--for both clinicians and surgeons--in the management of mitral valve disease in the context of left ventricular dysfunction. Given the current absence of clear guidelines, as well as of results from randomized trials comparing the outcome of different surgical strategies potentially available for this complex scenario, surgical decision making for these high-risk patients poses a real dilemma in the daily practice. The resulting surgical choices often represent a questionable combination of surgeons' personal feeling, local supplies, patients' life expectancy and risk/benefit ratios, opinions and statements of the experts, and so on. This review provides an overview of the present knowledge about the complex pathophysiology underlying functional mitral regurgitation, the different pathophysiology-guided surgical techniques suggested in the last decades, as well as the current results following these different surgical techniques.

Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest.

INTRODUCTION: Rewarming from deep hypothermic circulatory arrest (DHCA) produces calcium desensitization by troponin I (cTnI) phosphorylation which results in myocardial dysfunction. This study investigated the acute overall hemodynamic and metabolic effects of epinephrine and levosimendan, a calcium sensitizer, on myocardial function after rewarming from DHCA. METHODS: Forty male Wistar rats (400 to 500 g) underwent cardiopulmonary bypass (CPB) through central cannulation and were cooled to a core temperature of 13°C to 15°C within 30 minutes. After DHCA (20 minutes) and CPB-assisted rewarming (60 minutes) rats were randomly assigned to 60 minute intravenous infusion with levosimendan (0.2 µg/kg/min; n = 15), epinephrine (0.1 µg/kg/min; n = 15) or saline (control; n = 10). Systolic and diastolic functions were evaluated at different preloads with a conductance catheter. RESULTS: The slope of left ventricular end-systolic pressure volume relationship (Ees) and preload recruitable stroke work (PRSW) recovered significantly better with levosimendan compared to epinephrine (Ees: 85 ± 9% vs 51 ± 11%, P<0.003 and PRSW: 78 ± 5% vs 48 ± 8%, P<0.005; baseline: 100%). Levosimendan but not epinephrine reduced left ventricular stiffness shown by the end-diastolic pressure-volume relationship and improved ventricular relaxation (Tau). Levosimendan preserved ATP myocardial content as well as energy charge and reduced plasma lactate concentrations. In normothermia experiments epinephrine in contrast to Levosimendan increased cTnI phosphorylation 3.5-fold. After rewarming from DHCA, cTnI phosphorylation increased 4.5-fold in the saline and epinephrine group compared to normothermia but remained unchanged with levosimendan. CONCLUSIONS: Levosimendan due to prevention of calcium desensitization by cTnI phosphorylation is more effective than epinephrine for treatment of myocardial dysfunction after rewarming from DHCA.

Targeting urocortin signaling pathways to enhance cardioprotection: is it time to move from bench to bedside?

Despite the exponential growth in medical knowledge, cardiovascular diseases (CVDs) contribute to more than one-third of worldwide morbidity and mortality. A range of therapies already exist for established CVDs, although there is significant interest in further understanding their pathogenesis. The urocortins (Ucns) are peptide members of the corticotrophin-releasing factor family, a group of evolutionary conserved peptides with homologues in fish, amphibians and mammals and considered to play a pivotal role in energy homeostasis and local tissue repair. A number of preclinical studies in vitro, in-vivo and ex-vivo have defined a multifaceted effect of Ucns on the cardiovascular system. Different G-protein coupled signaling and protein-kinase pathways have been shown to be activated by Ucns, together with different transcriptional and translational effects, all of which preferentially converge on the mitochondria, where the modulation of apoptosis is considered their principal action. It has been demonstrated in experimental models, and consequentially suggested in human diseases, that Ucn-mediated inhibition of apoptosis can be exploited for the improvement of both therapeutic and preventative strategies against CVDs. Specifically, some unavoidable iatrogenic ischemia/reperfusion (I/R) injuries, e.g. during cardiac surgery or percutaneous coronary angioplasty, may greatly benefit from the anti-apoptotic effect of Ucns. However, few studies on the topic have been employed in humans to date. Therefore, this review will focus on the different intra-cellular mechanisms of action of Urocortins, and detail the different Ucn-mediated pathways identified so far. It will also highlight the limited evidence already existing in human clinical and surgical settings, as well as emphasize the potential uses of Ucns in human cardiac pathology.

Pulsatile flow decreases gaseous micro-bubble filtering properties of oxygenators without integrated arterial filters during cardiopulmonary bypass.

OBJECTIVES: Cardiopulmonary bypass (CPB) has a risk of embolic injury with an important role of gaseous micro-bubbles (GMBs), coming from CPB-circuit. Pulsatile perfusion (PP) can provide specific conditions for supplementary GMB-activity with respect to non-pulsatile (NP). We aimed to test GMB-filtering properties of three modern oxygenators under pulsatile and non-pulsatile conditions. METHODS: Seventy-eight patients undergoing on-pump myocardial revascularization were randomized prospectively into three equal groups according to the oxygenator model used during CPB. Terumo Capiox-FX25, Sorin Synthesis or Maquet Quadrox-i-Adult membrane oxygenators were tested. Each group was divided equally to undergo PP or NP. GMBs were counted by means of a GAMPT-BCC200 bubble-counter with two probes placed at preoxygenator and arterial post-filter positions. Results were evaluated in terms of GMB-volume, GMB-number, amount of large over-ranged GMBs, a series of filtering indices and major neurological outcomes. RESULTS: PP decreased GMB-filtering properties of the tested oxygenators. Those with integrated filters (CAPIOX-FX25 and SYNTHESIS) did not show significant differences between perfusion groups, while QUADROX-i oxygenator with external arterial filter showed significantly higher GMB-volume (P < 0.001), GMB-number (P < 0.001) and amount of over-ranged bubbles (P < 0.001) detected in arterial line during PP. Despite the differences in filtering capacity of all circuits with both types of perfusion, no important differences in clinical outcomes and major neurological events were observed. CONCLUSIONS: Pulsatile flow decreases gaseous micro-bubble filtering properties of oxygenators without integrated arterial filters during CPB. PP requires specially designed circuit components to avoid the risk of additional GMB delivery.

Effects of angiotensin II type 1 receptor antagonist and temperature on prolonged cardioplegic arrest in neonatal rat myocytes.

Cardioplegic arrest is a model of ischemia/reperfusion injury and results in the death of irreplaceable cardiac myocytes by a programmed cell death or apoptosis. Signal transducers and activators of transcription (STAT) signaling pathways play an important role in the modulation of apoptosis after ischemia and reperfusion. Angiotensin II type 1 (AT1) receptor antagonist added to cardioplegia could represent an additional modality for enhancing myocardial protection during cardioplegic arrest. To test that hypothesis, we studied the effect of AT1 receptor antagonism and cardioplegia temperature perfusion on STATs modulation during cardioplegic arrest in neonatal rat hearts. Isolated, nonworking hearts (n = 4 per group) from neonatal rats were perfused aerobically in the Langendorff mode according to the following scheme: Dulbecco's Modified Eagle's Medium solution (Group 1); cold (4°C) modified St. Thomas' Hospital no. 2 (MSTH2) cardioplegic solution (Group 2); cold (4°C) MSTH2 cardioplegic solution plus AT1 antagonist (Valsartan) (Group 3); and warm (34°C) MSTH2 cardioplegic solution (Group 4). Thus, myocytes were isolated by enzymatic digestion, and STAT1, STAT2, STAT3, and STAT5 were investigated in Western blot studies. Times to arrest after cardioplegia were 6-10 s for all groups with the exception of Group 1 (spontaneous arrest after 12-16 s). Total cardioplegia delivery volume was about 300 mL in 15 min. Perfusion with cold MSTH2 supplemented with AT1 receptor antagonist (Group 3) induced a significant reduction in STAT1, STAT2, and STAT5 tyrosine phosphorylation versus other groups (P < 0.05). The decreased activation of STAT1, STAT2, and STAT5 observed in Group 3 was accompanied by reduction of interleukin-1ß (P < 0.05). On the other hand, STAT3 activation was significantly reduced in Groups 1 and 4 (P < 0.05). Only perfusion with AT1 receptor antagonist supplemented with cold MSTH2 significantly decreases the inflammatory response of the neonatal rat cardiomyocytes without affecting antiapoptotic influence provided by activation of STAT3. Therefore, AT1 receptor antagonist could play a pivotal role in cytoprotective effect and cardiac recovery in neonates and infants.