Ricardo Zalaquett

Effects of extracorporeal circulation on renal function in coronary surgical patients

We prospectively studied perioperative changes of renal function in 12 previously normal patients (plasma creatinine <1.5 mg/dL) scheduled for elective coronary surgery. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured with inulin and125 I-hippuran clearances before induction of anesthesia, before cardiopulmonary bypass (CPB), during hypo- and normothermic CPB, after sternal closure, and 1 h postoperatively. Renal and systemic vascular resistances were calculated. Urinary N-acetyl-beta-D-glucosaminidase (NAG) and plasma and urine electrolytes were measured, and free water, osmolal, and creatinine clearances, and fractional excretion of sodium and potassium were calculated before and after surgery.125 I-hippuran clearance was lower than normal in all patients before surgery. During hypothermic CPB, ERPF increased significantly (from 261 +/- 107 to 413 +/- 261 mL/min) and returned toward baseline values during normothermia. GFR was normal before and after surgery and decreased nonsignificantly during CPB. Filtration fraction was above normal before surgery and decreased significantly during CPB (0.38 +/- 0.09 to 0.18 +/- 0.06). Renal vascular resistance (RVR) was high before surgery and further increased after sternotomy (from 18,086 +/- 6849 to 30,070 +/- 24,427 dynes centered dot s centered dot cm-5), decreasing during CPB to 13,9647 +/- 14,662 dynes centered dot s centered dot cm-5. Urine NAG, creatinine, and free water clearances were normal in all patients both pre- and postoperatively. Osmolal clearance and fractional excretion of sodium increased postoperatively from 1.54 +/- 0.06 to 12.47 +/- 11.37 mL/min, and from 0.44 +/- 0.3 to 6.07 +/- 6.27, respectively. We conclude that renal function does not seem to be adversely affected by CPB. Significant functional alterations, such as decreased ERPF and increased RVR, were found before and during surgery, preceding CPB. These periods could contribute to postoperative renal dysfunction. (Anesth Analg 1995;81:446-51)

Adenosine 5′-triphosphate and neuropeptide Y are co-transmitters in conjunction with noradrenaline in the human saphenous vein

Human saphenous veins were used to assess the cooperative participation of adenosine 5‐triphosphate (ATP), neuropeptide Y (NPY), and noradrenaline (NA) in the vasomotor responses elicited following electrical depolarization of the perivascular nerve terminals. Rings from recently dissected human biopsies were mounted to record isometric muscular contractions; the motor activity elicited in the circular muscle layer following electrical depolarization (2.5–20 Hz, 50 V, 0.5 msec) were recorded. Incubation of the biopsies with either 100 nM tetrodotoxin (TTX) or 1 μM guanethidine abolished the vasomotor response elicited by electrical nerve depolarization. The independent application of either ATP or NA to vein rings induced concentration‐dependent contractions. Tissue incubation with 30 μM suramin or 10 nM prazosin produced 10 fold rightward displacements of the α,β‐methylene ATP and NA concentration‐response curves respectively. NPY contracted a limited number of biopsies, the vasoconstriction elicited was completely blocked by 1 μM BIBP 3226. A 5 min incubation of the biopsies with 10–100 nM NPY synergized, in a concentration‐dependent fashion, both the ATP and the ATP analogue‐induced contractions. Likewise, tissue preincubation with 10 nM NPY potentiated the vasomotor responses evoked with 20–60 nM NA. Neither suramin, BIBP 3226, nor prazosin was individually able to significantly modify the derived frequency‐tension curves. In contrast, the co‐application of 30 μM suramin and 10 nM prazosin or 30 μM suramin and 1 μM BIBP 3226, elicited a significant (P<0.01) downward displacement of the respective frequency‐tension curves. The simultaneous application of the three antagonists–30 μM suramin, 1 μM BIBP 3226 and 10 nM prazosin–caused a significantly greater displacement of the frequency‐tension curve than that achieved in experiments using two of these antagonists. Electrically‐evoked vasomotor activity is blocked to a larger extent by tissue incubation with 2.5 μM chloroethylclonidine and 30 μM suramin rather than with 10 nM 5 methyl urapidil and 30 μM suramin. As a result, the α1‐adrenoceptor involved in the vasomotor activity has tentatively been associated with the α1B adrenoceptor family subtype. Results support the physiological role of ATP in sympathetic neurotransmission. The present results are consistent with the working hypothesis that human sympathetic vasomotor reflexes involve the coordinated motor action of ATP, NPY, and NA acting on vascular smooth muscle cells. The present results support the concept of sympathetic co‐transmission in the human saphenous vein.

Renal protection in patients undergoing cardiopulmonary bypass with preoperative abnormal renal function

We prospectively studied the effects of renal protection intervention in 17 patients with preoperative abnormal renal function (plasma creatinine >1.5 mg/dL) scheduled for elective coronary surgery. Patients were randomized to either dopamine 2.0 micro g [center dot] kg-1 [center dot] min-1 (Group 1

Impaired cardiac autophagy in patients developing postoperative atrial fibrillation

OBJECTIVES Postoperative atrial fibrillation (POAF) is a common complication after on-pump heart surgery. Several histologic abnormalities, such as interstitial fibrosis and vacuolization, have been described in atrial samples from patients developing POAF. This ultrastructural remodeling has been associated with the establishment of a proarrhythmic substrate. We studied whether atrial autophagy is activated in patients who develop POAF. METHODS A total of 170 patients in sinus rhythm who had undergone elective coronary artery bypass grafting were included. Systemic inflammatory markers were measured at baseline and 72 hours after surgery. During the procedure, samples of the right atrial appendages were obtained for evaluation of remodeling by light and electron microscopy. Protein ubiquitination and autophagy-related LC3B processing were assessed by Western blot. RESULTS Of these patients, 22% developed POAF. The level of high-sensitivity C-reactive protein, fibrosis, inflammation, myxoid degeneration, and ubiquitin-aggregates in the atria did not differ between patients with and without POAF. Electron microphotographs of those with POAF showed a significant accumulation of autophagic vesicles and lipofuscin deposits. Total protein ubiquitination was similar in the patients with and without POAF, but LC3B processing was markedly reduced in those with POAF, suggesting a selective impairment in autophagic flow. CONCLUSIONS This study provides novel evidence that ultrastructural atrial remodeling characterized by an impaired cardiac autophagy is present in patients developing POAF after coronary artery bypass surgery.

Defective insulin signaling and mitochondrial dynamics in diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a common consequence of longstanding type 2 diabetes mellitus (T2DM) and encompasses structural, morphological, functional, and metabolic abnormalities in the heart. Myocardial energy metabolism depends on mitochondria, which must generate sufficient ATP to meet the high energy demands of the myocardium. Dysfunctional mitochondria are involved in the pathophysiology of diabetic heart disease. A large body of evidence implicates myocardial insulin resistance in the pathogenesis of DCM. Recent studies show that insulin signaling influences myocardial energy metabolism by impacting cardiomyocyte mitochondrial dynamics and function under physiological conditions. However, comprehensive understanding of molecular mechanisms linking insulin signaling and changes in the architecture of the mitochondrial network in diabetic cardiomyopathy is lacking. This review summarizes our current understanding of how defective insulin signaling impacts cardiac function in diabetic cardiomyopathy and discusses the potential role of mitochondrial dynamics.

Systemic vascular cell adhesion molecule-1 predicts the occurrence of post-operative atrial fibrillation

BACKGROUND Post-operative atrial fibrillation occurs in 30% of patients after on-pump heart surgery and is associated to elevated inflammatory markers. We have evaluated if the systemic biomarkers of inflammation and endothelial damage, vascular cell adhesion molecule-1 (VCAM-1) and soluble thrombomodulin may help in identifying patients prone to development of post-operative atrial fibrillation. METHODS One hundred and forty-four patients in sinus rhythm submitted to elective coronary artery bypass surgery. Systemic inflammatory, oxidative stress and endothelial damage markers were measured at baseline and 72 h after surgery. During the procedure, a sample of the right atrial appendage was obtained for histochemistry. Electrocardiogram was monitored for 72 h after surgery for event adjudication. RESULTS 22% of the patients developed post-operative atrial fibrillation. Baseline systemic inflammatory markers did not differ between patients with or without post-operative atrial fibrillation. However, baseline plasma VCAM-1 and thrombomodulin levels were significantly higher in patients who developed post-operative atrial fibrillation. After adjustment for age, gender, comorbidities and concurrent medication, circulating VCAM-1 remained as an independent predictor for post-operative atrial fibrillation development. No association was observed between systemic plasma VCAM-1 and VCAM-1 tissue expression in the right atrial appendage. CONCLUSIONS In patients undergoing coronary artery bypass surgery, elevated VCAM-1 levels predict a higher risk for post-operative atrial fibrillation. Plasma VCAM-1 elevation is not related to its expression in the right atria, suggesting that systemic endothelial damage rather than local changes pre-exist in patients who develop the arrhythmia.

Comparison of two doses of aprotinin in patients receiving aspirin before coronary bypass surgery

This study was designed to evaluate efficacy and tolerability of two different doses of aprotinin in patients receiving aspirin before undergoing coronary artery bypass grafting. Forty-two patients were randomized to receive either placebo (group I), or aprotinin in doses of 4 000 000 KIU (group II) or 6 000 000 KIU (group III). Drug efficacy was determined by measuring postoperative blood loss and transfusion of blood products. Both doses were effective in reducing blood loss and transfusion requirements. Blood loss through thoracotomy drainage was 450 ± 224, 182 ± 144, 142 ± 98 ml, respectively, for control and treatment groups II and III (p = 0.0001). The numbers of patients with blood transfusions were seven (50%), two (17%) and two (17%) for group I and treatment groups II and III, respectively (p = 0.10). Tolerability was excellent and complications few and reversible. In conclusion, high and medium doses of aprotinin were well tolerated and reduced bleeding and transfusion requirements in patients submitted to coronary bypass surgery under the effects of aspirin.

Persistencia del estrés oxidativo postrasplante cardíaco: estudio comparativo entre pacientes con trasplante cardíaco y con insuficiencia cardíaca crónica estable

Introduccion y objetivo Existe estres oxidativo en pacientes con insuficiencia cardiaca cronica (ICC). El trasplante cardiaco, alternativa terapeutica importante en estos pacientes, podria disminuir el estres oxidativo al mejorar la funcion cardiaca. Nuestro objetivo fue evaluar el estres oxidativo postrasplante cardiaco. Pacientes y metodo Fueron estudiados 3 grupos experimentales: a) trasplantados cardiacos, sin evidencia de rechazo (n = 11); b) pacientes con ICC capacidad funcional III de la NYHA (n = 19), y c) sujetos controles sanos (n = 14). El estres oxidativo se evaluo determinando valores plasmaticos de malondialdehido (MDA), y actividades de glutation peroxidasa (GSH-Px), catalasa (CAT) y superoxido dismutasa (SOD). Resultados Las caracteristicas demograficas fueron similares entre los grupos. El tiempo postrasplante fue 20,0 ± 4,8 meses. Los valores de MDA en trasplantados y con ICC fueron significativamente mayores que en sujetos normales (3,35 ± 0,8; 3,27 ± 1,7, y 0,90 ± 0,3 µM, respectivamente). La actividad de GSH-Px aumento en trasplantados respecto al grupo control (0,40 ± 0,07 y 0,33 ± 0,05 U/g Hb, respectivamente). La actividad de SOD fue menor en trasplantados respecto al grupo control ICC (0,44 ± 0,1 frente a 0,87 ± 0,6 U/mg Hb). No hubo diferencias en las actividades de CAT entre trasplantados y pacientes con ICC. Conclusion Los pacientes sometidos a trasplante cardiaco tienen un aumento del estres oxidativo, evidenciado por una elevacion del MDA y por una disminucion de la actividad de SOD, a pesar de una mayor actividad de GSH-Px. Este aumento del estres oxidativo fue similar al encontrado en pacientes con ICC estable CF III de la NYHA, y se observo en ausencia de episodios reconocidos de infeccion o rechazo.

Revascularización miocárdica de la arteria descendente anterior con anastomosis mamaria con técnica clásica

Introduccion y objetivos Establecer los resultados obtenidos con la tecnica clasica de anastomosis de la arteria descendente anterior. Material y metodos Entre enero de 1982 y julio de 1997, 154 pacientes fueron sometidos a cirugia de revascularizacion de la arteria descendente anterior con mamaria usando tecnica clasica (esternotomia y circulacion extracorporea). Resultados En nuestro grupo no hubo mortalidad, infarto perioperatorio ni accidente vascular encefalico. Un paciente (0,6%) tuvo infeccion de la herida esternal y otro (0,6%) presento sangrado postoperatorio que requirio reoperacion. Se obtuvo un 100% de seguimiento entre 3 y 183 meses (promedio, 64,4 meses). La supervivencia actuarial global a los 5, 10 y 15 anos fue del 95,6 ± 2,1%; 92,1 ± 4% y 85,5 ± 7,5%, respectivamente, y la probabilidad actuarial de estar libre de muerte cardiaca fue de 99 ± 0,9%; 99% y 99%. La probabilidad actuarial de estar libre de infarto a los 5, 10 y 15 anos fue de 99 ± 0,9%, 99% ± 0,9% y 99%, y la de estar libre de angina del 95 ± 2,2%; 86,9 ± 4,9% y 74,5 ± 12,2%. Finalmente, la probabilidad actuarial de estar libre de reoperacion y de angioplastia a los 5, 10 y 15 anos fue del 99 ± 0,9%, 99%, 99% y 96,9 ± 1,7%, 91,4 ± 4.1% y 91,4 ± 4,1%, respectivamente. La cuenta hospitalaria promedio en el ultimo 10% de este grupo fue 199,8 UF (6.200 dolares). Conclusion La revascularizacion miocardica a la descendente anterior con arteria mamaria unica, con tecnica clasica, es un procedimiento seguro, de minimo riesgo, de bajo coste y de excelentes resultados a los 10 y 15 anos

Morbimortalidad precoz y alejada del reemplazo valvular aórtico con prótesis mecánica y biológica durante la última década: El estándar de oro

BACKGROUND There is a growing interest in alternative techniques for aortic valve replacement (AVR). Therefore it is important to have updated results of conventional AYR as a valid comparative standard. AIM To evaluate both perioperative and late morbidity and mortality in patients undergoing conventional AVR, with either mechanical (RVAm) or biological (RVAb) prostheses. PATIENTS AND METHODS Retrospective review of medical records and operative protocols of patients undergoing AVR between January 1995 and December 2005. Patients with previous cardiac surgery, aortic balloonplasty or simultaneous cardiovascular procedures were excluded. RESULTS During the study period, 788 patients underwent AVR and 317 met the inclusion criteria. Of the latter, 175 patients aged 13 to 83 years (63% males) were subjected to AVRm and 142 patients aged 49 to 87 years (64% males), were subjected to AVRb. Five (1.6%) patients died during the perioperative period (one AVRm and four AVRb). All were older than 65 years. Perioperative complications were recorded in 29 and 25% of patients in AVRm and AVRb groups, respectively (NS). During a median follow-up of six years, complications were recorded in 12 and 4% of patients in AVRm and AVRb groups, respectively (p <0.05). The actuarial survival for AVRm group at 1, 5 and 10 years, was 96, 92 and 87%, respectively. The figures for AVRb group were 95, 86 and 83%, respectively (NS). The 10 year reintervention free survival was 97% for the AVRm group and 84% for the AVRb (p <0.05). CONCLUSIONS Perioperative mortality and rates of complications of AVR in this series of patients are low, which compares favorably with other series.